Submissions for variant NM_001130987.2(DYSF):c.1465G>A (p.Glu489Lys)

gnomAD frequency: 0.01748  dbSNP: rs61740288

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen	RCV004998207	SCV005620322	benign	Autosomal recessive limb-girdle muscular dystrophy	2025-01-08	reviewed by expert panel	curation	The NM_003494.4: c.1369G>A variant in DYSF, which is also known as NM_001130987.2: c.1465G>A (p.Glu489Lys), is a missense variant predicted to cause substitution of glutamic acid by lysine at amino acid 457 (p.Glu457Lys). The filtering allele frequency of the variant is 0.02368 for European (non-Finnish) exome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 4291/251472), which is higher than the VCEP threshold of 0.003 (BA1). The SpliceAI score for this variant is 0.28 and the computational predictor REVEL gives a score of 0.41. Both of these scores are neither above nor below the thresholds predicting a damaging or benign impact (BP4/PP3 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)	RCV000080233	SCV000112128	benign	not specified	2012-11-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000080233	SCV000309643	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000710125	SCV000512915	benign	not provided	2019-04-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25312915, 22995991, 31862442, 20981092, 17698709, 27884173, 21522182, 25214167)
Athena Diagnostics	RCV000710125	SCV000613180	benign	not provided	2017-10-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550203	SCV000649604	benign	Qualitative or quantitative defects of dysferlin	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000550203	SCV001300835	uncertain significance	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080233	SCV002050942	likely benign	not specified	2021-12-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710125	SCV002544046	benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	DYSF: BS1, BS2
Genetic Services Laboratory, University of Chicago	RCV000080233	SCV000151013	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080233	SCV001743867	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000710125	SCV001797971	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000080233	SCV001929504	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001835673	SCV002079800	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2019-11-14	no assertion criteria provided	clinical testing