ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.8381A>T (p.Tyr2794Phe)

gnomAD frequency: 0.00001  dbSNP: rs750548574
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810643 SCV000950865 pathogenic Nemaline myopathy 2 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2794 of the NEB protein (p.Tyr2794Phe). This variant is present in population databases (rs750548574, gnomAD 0.004%). This missense change has been observed in individual(s) with nemaline myopathy (PMID: 25205138; Invitae). 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: 654638). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001731939 SCV001983545 uncertain significance not specified 2021-09-17 criteria provided, single submitter clinical testing Variant summary: NEB c.8381A>T (p.Tyr2794Phe) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 247004 control chromosomes. c.8381A>T has been reported in the literature in individuals affected with Nemaline Myopathy 2 (Lehtokari_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002507410 SCV002815274 uncertain significance Nemaline myopathy 2; Arthrogryposis multiplex congenita 6 2021-09-24 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003130061 SCV003811541 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV003467443 SCV004200097 likely pathogenic Arthrogryposis multiplex congenita 6 2024-03-19 criteria provided, single submitter clinical testing
GeneDx RCV003130061 SCV005326263 likely pathogenic not provided 2024-03-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Kiiski2015[thesis], 25205138)
Natera, Inc. RCV000810643 SCV001463529 uncertain significance Nemaline myopathy 2 2020-09-16 no assertion criteria provided clinical testing

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