Association Details

The following tables describe the variant and gene association details.

BaseSpace Variant Interpreter follows ACMG guidelines for classification.

Classification	Description
Pathogenic (P)	Segregates with disease in multiple unrelated cases with control data. The variant is in a highly conserved region. Functional studies or other evidence indicate a deleterious effect on gene expression.
Uncertain Clinical Significance-Likely Pathogenic (UCS-LP)	Meets reporting criteria for pathogenic variants, however insufficient evidence is available for unequivocal determination.
Uncertain Clinical Significance (UCS)	Nothing about this variant has been reported, or reported information is incomplete or contradictory.
Uncertain Clinical Significance-Likely Benign (UCS-LB)	Meets reporting criteria for benign variants, however insufficient evidence is available for unequivocal determination.
Benign (B)	Functionally normal. Reported at high frequency in control data and does not segregate with disease. The variant might be nonconserved and predicted to be tolerated.

BaseSpace Variant Interpreter follows ACMG guidelines for classification.

Classification	Description
Pathogenic (P)	Segregates with disease in multiple unrelated cases with control data. The variant is in a highly conserved region. Functional studies or other evidence indicate a deleterious effect on gene expression.
Likely Pathogenic (LP)	Reported in some case studies with or without control data. The variant is in a highly conserved region. Functional studies or other evidence highly suggest a deleterious effect on gene expression.
Variant of Unknown Significance (VUS)	Nothing about this variant has been reported, or reported information is incomplete or contradictory.
Likely Benign (LB)	Functionally normal. Reported in a few cases with little or no control data. The variant might be nonconserved and predicted to be tolerated. Based on disease prevalence and penetrance information, the variant frequency is higher than expected in the general population.
Benign (B)	Functionally normal. Reported at high frequency in control data and does not segregate with disease. The variant might be nonconserved and predicted to be tolerated.

Variant Classification (STRs)

Classification	Description
Expanded	The number of STRs is increased relative to the reference sequence.
Not Expanded	The number of STRs is decreased or unchanged relative to the reference sequence.

Gene Classification

BaseSpace Variant Interpreter follows the Clinical Genome gene-disease evidence guidelines for classification.

Classification	Description
Definitive	Evidence is repeatedly demonstrated and upheld over time.
Strong	Evidence has been independently demonstrated in separate studies.
Moderate	Clinical evidence and supporting experimental evidence are reported in at least one study.
Limited	At least one variant has plausible genetic evidence to support the association, with or without gene-level experimental data.
Conflicting	Conflicting evidence that disputes or refutes an assertion of gene-disease association has been reported.
No evidence	Evidence for a causal role for this gene in this disease has not been reported.

Mode of Inheritance

The disease mode of inheritance.

Mode of Inheritance	Description
Autosomal Dominant	The gene is on a nonsex chromosome. A single copy of the variant associated with disease is sufficient to cause the disease.
Autosomal Recessive	The gene is on a nonsex chromosome. Two copies of an abnormal gene must be present for disease to develop.
Autosomal Dominant/Recessive	A combination of autosomal dominant and autosomal recessive variants are associated with disease. The variant presentation may differ between autosomal dominant and autosomal recessive contexts.
X-Linked Dominant	A dominant gene is on the X chromosome.
X-Linked Recessive	A variant in a gene on the X chromosome causes a phenotype to be expressed in males and in females who are homozygous for the gene mutation.
X-Linked Not Specified	Inheritance of genes on the X chromosome, but it is not known if the gene is dominant or recessive.
Y-Linked	Inheritance of genes on the Y chromosome.
Complex	Two heterogenous recessive alleles are present at a locus that can cause disease.
Inconclusive	The inheritance cannot be determined.
Mitochondrial	A mutation in mitochondrial DNA.
Unknown	The mode of inheritance is not known.

Mechanism

Mechanism	Description
Loss of Function	The variant association is expected to result in a decrease in function.
Gain of Function	The variant association is expected to result in an increase in function.

Other Details

The following table lists other details about variants in Knowledge Network.

Detail	Description
Penetrance	The proportion of individuals who carry the variant and express the related disease.
Confidence	The level of confidence in the causality for the association.
Curator Summary	The description of the association provided by the curator.