Modes of inheritance

Symbol Term Description
AD Autosomal dominant Pattern of inheritance in which a single mutated allele located on one of the 22 autosomes (non-sex chromosomes) is sufficient to express the phenotype. This mutated allele is present in both the somatic and the germline.
AD/AR Autosomal inheritance The disease phenotype may be expressed with only one mutated gene allele (located on one of the 22 autosomes - non-sex chromosomes) - Autosomal dominant. However in some cases both gene alleles need to be mutated to express the phenotype (autosomal recessive). That is, heterozygous carriers may not always present clinical manifestations, but carriers of 2 mutated alleles do. Generally, the phenotype of individuals carrying biallelic mutations is more severe than that of those carrying only one mutated allele.
AR Autosomal recessive Pattern of inheritance in which two mutated alleles of the same gene located on one of the 22 autosomes (non-sexual chromosomes) are needed to express the phenotype. These mutated alleles is present in both the somatic and the germline.
XLD X-linked dominant Pattern of inheritance in which a single mutated allele on the X chromosome is sufficient to express the phenotype. The phenotype is more consistently and severely expressed in hemizygous boys (having only one copy of the gene) than in heterozygous girls.
XLR X-linked recessive Pattern of inheritance in which two mutated alleles on the X chromosome are needed to express the phenotype. The phenotype is expressed in hemizygous boys (having only one copy of the gene) and homozygous girls.
XL X-linked Pattern of inheritance in which a single mutated allele on the X chromosome is sufficient to express the phenotype in males. Females can be unaffected or mildly affected depending on the degree of skewed X inactivation.
YL Y-linked Pattern of inheritance in which a single mutated allele on the Y chromosome is sufficient to express the phenotype. The transmission is exclusively paternal.
MT Mitochondrial Pattern of inheritance in which a mutation in one of the mitochondrial genes is sufficient to express the phenotype. The transmission is exclusively maternal.
So Somatic A trait or disorder that results from a de novo mutation occurring exclusively in the somatic line after conception, rather than being inherited from a preceding generation. Somatic mutations occur in all body tissues throughout life and are not present in the germline from which the individual developed and cannot be transmitted to the offspring.
DR Digenic recessive A disorder caused by homozygous or compound heterozygous mutation in one gene and a heterozygous mutation in a second gene.

Variant effect

Term Alt. terms Description Value
Antimorphic DN | Dominant Negative loss of function | LOF A mutation whose gene product adversely affects the normal, wild-type gene product within the same cell. This usually occurs if the mutant product can still interact with the WT product or with the same elements as the WT product. Example: In a protein that is functional as a dimer. Loss of function is >50%. -2.5
Amorphic LOF | complete loss of function A mutation that causes complete (100%) or nearly complete loss of gene/protein function at the molecular and cellular level. -2.0
Loss of function LOF | Loss-of-function A mutation that results in loss of protein/gene function, but it is not clear whether the loss is partial (hypomorphic) or complete (amorphic), or the loss of function is somewhere in between. -1.5
Hypomorphic LOF | partial loss of function A mutation that causes a partial loss of gene/protein function at the molecular and cellular level. Loss of function is < 50%. -1.0
Conflicting unknown | uncertain | contradictory The consequence of the variant has been experimentally addressed but results from different tests or groups are contradictory -0.5
Not tested untested | unexamined | not evaluated The consequence of this variant on the protein's function and/or structure, and its effect at the cellular level has not been functionally tested yet. 0.0
Isomorphic silent | synonymous | wildtype A silent synonymous or missense mutation with identical, or not significantly different, gene expression and protein function as the original wild type allele. 0.5
Hypermorphic(mild) moderate GOF | mild gain of function | mild GOF A mutation whose gene product causes a moderare but significant increase in normal gene-product function/dosage/activity at the molecular and cellular level. 1.0
Hypermorphic GOF | gain of function | gain-of-function A mutation whose gene product causes an increase in normal gene-product function/dosage/activity at the molecular and cellular level. 2.0
Neomorphic GOF | gain of function | gain-of-function A mutation whose gene product causes a novel or improved gene-product function/dosage/activity at the molecular and cellular level. 2.5

Mechanisms of action (diseases)

Term Description
Loss of Function Disease caused by the loss of the normal biological function of a protein. Often this is due to nonsense or frameshift mutations that introduce premature stop codons. Due to nonsense-mediated decay of the resulting mRNAs, most premature stop codons will result in no protein being produced, rather than a truncated protein. However, thereare also many examples of loss-of-function mutations that change the amino acid sequence and result in nonfunctional protein products. These mutations can cause a complete loss of function (amorphic), analogous to a protein null mutation, or only a partial loss of function (hypomorphic).
Dominant Negative Disease is caused by mutations that involve the mutant protein directly or indirectly blocking the normal biological function of the wild-type protein (antimorphic). They can thus cause a disproportionate (>50%) loss of function, even though only half of the protein is mutated.
Haploinsufficiency A single copy of the wild-type allele of a gene in combination with a mutant allele is insufficient to produce enough gene product (protein) to preserve normal function.
Gain of Function Disease is caused because the mutant protein does something different than the wild-type protein. Often, these mutations cause disease by increasing protein activity (hypermorphic) or introducing a completely new function (neomorphic), but the specific molecular mechanisms underlying gain-of-function mutations can be complex.

Zygosities

Symbol Term Alt. terms Description Ontology ID
HET Heterozygous Heterozygote In a diploid organism, it refers to a cell that has two different alleles (wild-type and mutant) for a specific gene or locus. The cell or organism may be heterozygous or a heterozygote for the allele in question. Heterozygosity refers to a specific genotype. GENO:0000135
HOM Homozygous Homozygote A diploid cell or organism is homozygous for a gene or locus when both alleles are identical for that specific region of DNA. For instance a homozygote can have two wild-type or two identically mutated gene alleles. GENO:0000136
HEM Hemizygous Hemizygote Hemizygous is a condition in which only one copy of a gene or DNA sequence is present in diploid cells. Males are hemizygous for most genes on sex chromosomes, having only one X and one Y chromosome. Hemizygosity is also observed when one copy of a gene is deleted. GENO:0000134
mHOM Homoplasmic Homoplasmy An allelic state where a single allele exists at a particular locus in the organellar genome (mitochondrial or plastid) of a cell/organism. GENO:0000602
mHET Heteroplasmic Heteroplasmy An allelic state where more than one type of allele exists at a particular locus in the organellar genome (mitochondrial or plastid) of a cell/organism. GENO:0000603
HOM? Presumed homozygote presumed homozygous | suspected homozygous | homozygous? Affected individual who has affected siblings with a similar phenotype and carrying presumably the same homozygous mutation but that cannot be demonstrated because DNA was not available due to early death or other reasons.
OC Obligate heterozygote very likely heterozygous carrier | obligate carrier An individual, affected or unaffected, who must carry the gene mutation found in the index case(s) based on the phenotype segregation throughout the family pedigree.
WT Wild type wild-type allele | wild_type allele | wild type allele An allele representing a highly common varaint (typically >99% in a population), that typically exhibits canonical function, and against which rare and/or non-functional mutant alleles are compared. The notion of wild-type alleles is more common in model organism databases, where specific mutations are generated against a wild-type reference feature. Wild-type alleles are typically - but not always - used as reference alleles in sequence comparison/analysis applications. More than one wild-type sequence can exist for a given feature, but typically only one allele is deemed wild-type in the context of a single dataset or analysis. GENO:0000501
Som Somatic somatic mutation | acquired mutation A genetic change that occurs after conception in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. This acquired alteration is passed on to the progeny of the mutated cell in the course of cell division. Somatic mutations are frequently caused by environmental factors, such as exposure to ultraviolet radiation or to certain chemicals. Somatic mutations might cause various diseases, including cancer. GENO:0000882
Mos Mosaic mosaic mutation | mosaicism An individual containing two or more populations of genetically different cells that arose from a single zygote during embryogenesis. Therefore a specific mutation may only be present in a subset of body tissues. Mosaicism could affect both the somatic and the germ lines. GENO:0000964
PC Presumed heterozygote possible heterozygous carrier An individual, affected or unaffected, who possibly carries the gene mutation found in the index case(s) based on the phenotype segregation throughout the family pedigree.