Submissions for variant NM_001130987.2(DYSF):c.3119G>A (p.Arg1040Gln)

gnomAD frequency: 0.02614  dbSNP: rs34211915

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen	RCV004998212	SCV005620325	benign	Autosomal recessive limb-girdle muscular dystrophy	2025-01-08	reviewed by expert panel	curation	The NM_003494.4: c.3065G>A variant in DYSF, which is also known as NM_001130987.2: c.3119G>A p.(Arg1040Gln), is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 1022 (p.Arg1022Gln). The filtering allele frequency of the variant is 0.03338 for African/African American genome chromosomes in gnomAD v3.1.2 (the lower threshold of the 95% CI of 3745/152196), which is higher than the VCEP threshold of 0.003 (BA1). The SpliceAI score for this variant is 0.02, suggesting it does not impact splicing. However, the computational predictor REVEL gives a score of 0.39, which is above the LGMD VCEP threshold predicting a benign impact on DYSF function (≤0.1; BP4 not met). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BA1.
Eurofins Ntd Llc (ga)	RCV000080265	SCV000112160	benign	not specified	2012-07-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000080265	SCV000309665	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000080265	SCV000512917	benign	not specified	2016-01-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526480	SCV000649648	benign	Qualitative or quantitative defects of dysferlin	2025-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000526480	SCV001300242	likely benign	Qualitative or quantitative defects of dysferlin	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080265	SCV002050940	likely benign	not specified	2021-12-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001699117	SCV002544048	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	DYSF: PM5, BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001699117	SCV005257062	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000080265	SCV000151022	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Natera, Inc.	RCV001276438	SCV001462783	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-09-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080265	SCV001741993	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001699117	SCV001925150	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699117	SCV001928133	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001699117	SCV002035543	likely benign	not provided		no assertion criteria provided	clinical testing