Submissions for variant NM_001130987.2(DYSF):c.5743G>A (p.Asp1915Asn)

gnomAD frequency: 0.00257  dbSNP: rs115013641

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080307	SCV000334275	benign	not specified	2017-06-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000710132	SCV000512919	benign	not provided	2018-07-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25525159, 21522182, 17897828, 22046204, 24838345)
Athena Diagnostics	RCV000710132	SCV000613216	benign	not provided	2018-11-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081966	SCV000649728	benign	Qualitative or quantitative defects of dysferlin	2025-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710132	SCV001152343	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	DYSF: BS2
Illumina Laboratory Services, Illumina	RCV001081966	SCV001303332	likely benign	Qualitative or quantitative defects of dysferlin	2017-07-31	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine 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	RCV000080307	SCV002500092	benign	not specified	2022-03-04	criteria provided, single submitter	clinical testing	Variant summary: DYSF c.5626G>A (p.Asp1876Asn) results in a conservative amino acid change located in the C2 domain (IPR000008) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 251492 control chromosomes, predominantly at a frequency of 0.0087 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in DYSF causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.0031), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign (n=4) and likely benign (n=3). Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002490698	SCV002798953	likely benign	Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset	2022-04-27	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000710132	SCV005257528	likely benign	not provided		criteria provided, single submitter	not provided
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000710132	SCV001955359	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000080307	SCV001970387	benign	not specified		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV001787038	SCV002029125	not provided	Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset; Miyoshi myopathy		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 01-23-2012 by Lab or GTR ID 1012. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000710132	SCV002036493	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831822	SCV002080335	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2019-11-15	no assertion criteria provided	clinical testing