ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.147+1G>A

dbSNP: rs2082833010
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology RCV001249863 SCV001189953 pathogenic Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset 2020-03-06 criteria provided, single submitter clinical testing The c.147+1G>A variant is a splice-site variant and not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD). The variant is not present in our in-house exome database. The variant was not reported earlier to OMIM, ClinVar or Human Genome Mutation Database (HGMD) in other affected individuals. In-silico pathogenicity prediction programs like HSF3, MutationTaster2, CADD etc. predicted this variant to be likely deleterious by altering splicing. The variant has been identified along with another heterozygous variant in this gene (NM_001130987.2:c.5246delA), that causes a frameshift in exon 46. The variant has been classified as pathogenic as per ACMG guidelines.
Labcorp Genetics (formerly Invitae), Labcorp RCV003574861 SCV004293937 pathogenic Qualitative or quantitative defects of dysferlin 2022-10-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with DYSF-related conditions (PMID: 27347015, 27647186). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 973349). 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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