ClinVar Miner

Submissions for variant NM_001199973.2(RPL36A-HNRNPH2):c.300+3109_300+3112del

dbSNP: rs869312426
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192398 SCV001360484 pathogenic Fabry disease 2019-05-29 criteria provided, single submitter clinical testing Variant summary: GLA c.803_806delTAGT (p.Leu268X) 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.901C>T (p.Arg301X), c.1021G>T(p.Glu341X)). The variant was absent in 182745 control chromosomes (gnomAD) but has been reported in the literature in male patients affected with Fabry Disease as well as in symptomatic heterozygous females (Juchniewicz_2018, Wijburg_2014, Lee_2000). Taken together, these data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001192398 SCV001587058 pathogenic Fabry disease 2023-05-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu268*) in the GLA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 11076046, 12175777). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1323012). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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