ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.394G>A (p.Asp132Asn)

gnomAD frequency: 0.00001  dbSNP: rs759893630
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687312 SCV000814874 uncertain significance Costello syndrome 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 132 of the HRAS protein (p.Asp132Asn). This variant is present in population databases (rs759893630, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 567281). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt HRAS function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV000788501 SCV000927645 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782512 SCV005394425 uncertain significance not specified 2024-09-30 criteria provided, single submitter clinical testing Variant summary: HRAS c.394G>A (p.Asp132Asn) results in a conservative amino acid change located in the Small GTP-binding domain (IPR005225) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251164 control chromosomes, predominantly at a frequency of 3.5e-05 within the Non-Finnish European subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.394G>A in individuals affected with Costello Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 567281). Based on the evidence outlined above, the variant was classified as uncertain significance.

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