ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.155C>A (p.Ser52Ter) (rs987036804)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430851 SCV000516069 pathogenic not provided 2015-03-19 criteria provided, single submitter clinical testing The S52X nonsense variant in the HEXA gene has also been reported previously in association with infantile-onset Tay-Sachs disease (McGinniss et al., 2002; Zampieri et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret S52X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000780337 SCV000917517 pathogenic Tay-Sachs disease 2018-07-09 criteria provided, single submitter clinical testing Variant summary: HEXA c.155C>A (p.Ser52X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.187G>T, p.Glu63X and c.1168C>T, p.Gln390X). The variant allele was found at a frequency of 1.2e-05 in 246232 control chromosomes. c.155C>A has been reported in the literature in individuals affected with Tay-Sachs Disease (Gort_2012, McGinniss_2002, Zampieri_2012). At least one patient tested in these studies had <10% enzyme activity reported in the publication. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000780337 SCV001211559 pathogenic Tay-Sachs disease 2019-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser52*) in the HEXA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Tay Sachs disease (PMID: 22441121). ClinVar contains an entry for this variant (Variation ID: 379311). Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). For these reasons, this variant has been classified as Pathogenic.

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