ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.739C>T (p.Arg247Trp)

gnomAD frequency: 0.00190  dbSNP: rs121907970
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000242608 SCV000304643 benign not specified criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000279029 SCV000331537 other not provided 2016-04-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000279029 SCV000493276 uncertain significance not provided 2020-07-01 criteria provided, single submitter clinical testing
Invitae RCV000549043 SCV000629536 other Tay-Sachs disease 2017-05-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000242608 SCV000697173 benign not specified 2021-12-27 criteria provided, single submitter clinical testing Variant summary: HEXA c.739C>T (p.Arg247Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 251482 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is slight higher than the estimated maximal expected allele frequency for a pathogenic variant in HEXA causing Tay-Sachs Disease phenotype (0.0014). About 35% of non-Jewish individuals identified as heterozygotes by HEX A enzyme-based testing are carriers of a pseudodeficiency allele. About 2% of Jewish individuals identified as heterozygotes by HEX A enzyme-based testing in carrier screening programs are actually heterozygous for the variant of interest. c.739C>T is widely accepted in the field as benign pseudodeficient allele. c.739C>T has been reported in the literature in individuals affected with Tay-Sachs Disease. These reports do not provide unequivocal conclusions about association of the variant with Tay-Sachs Disease. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Cao_1997). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000279029 SCV001812632 benign not provided 2018-01-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31692161, 29482223, 26990548, 19858779, 22975760, 1384323, 17259242, 9169471)
OMIM RCV000004128 SCV000024294 pathogenic Beta-hexosaminidase a, pseudodeficiency of 1993-08-01 no assertion criteria provided literature only

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