rs387906309

badMag 9.0

This is a frameshift variant variant in the HEXA gene.

Key Literature Trait Associations

Tay-Sachs Disease

rs387906309 (c.1274_1277dup, p.Tyr427fs) is a pathogenic frameshift insertion in HEXA that abolishes beta-hexosaminidase A activity, causing GM2 gangliosidosis. In homozygotes or compound heterozygotes, it produces classic infantile Tay-Sachs disease, characterized by progressive neurodegeneration beginning at 3–6 months, with death typically by age 4–5. As a carrier (heterozygote), the variant confers no disease but a ~1/30 carrier frequency in Ashkenazi Jews — roughly 10-fold above the general population — making it a principal target of preconception carrier screening. ClinVar classifies this variant as Pathogenic with criteria provided by multiple independent submitters.

Myerowitz R et al. “The major defect in Ashkenazi Jews with Tay-Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase.” The Journal of Biological Chemistry (1988)

Allele DUPGATA

OR —

p —

Candidate gene study

Ashkenazi Jewish

Lew R et al. “Tay-Sachs disease preconception screening in Australia: self-knowledge of being an Ashkenazi Jew predicts carrier state better than does ancestral origin, although there is an increased risk for c.1421 + 1G > C mutation in individuals with South African heritage.” Journal of Community Genetics (2011)

Allele DUPGATA

OR —

p —

N 4,105

Preliminary work

Ashkenazi Jewish (Australia)

Frisch A et al. “Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.” Human Genetics (2004)

Allele DUPGATA

OR —

p —

N 55

Candidate gene study

Ashkenazi Jewish

Myerowitz R et al. “Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene.” Human Mutation (1997)

Allele DUPGATA

OR —

p —

Candidate gene study

multi-ancestry

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ClinVar annotation

Pathogenic★★★☆

HEXA-related disorder; Inborn genetic diseases; Intellectual disability; Tay-Sachs disease (TSD); Tay-Sachs disease, variant AB

rs387906309

Key Literature Trait Associations

Tay-Sachs Disease

ClinVar annotation

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