Submissions for variant NM_001130987.2(DYSF):c.3898-4C>G

gnomAD frequency: 0.00001  dbSNP: rs555206040

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen	RCV004999251	SCV005620334	likely benign	Autosomal recessive limb-girdle muscular dystrophy	2025-01-09	reviewed by expert panel	curation	The NM_003494.4: c.38844-4C>G variant in DYSF, which is also known as NM_001130987.2: c.3898-4C>G, is an intronic variant located in intron 34 of 54. The filtering allele frequency for this variant is 0.001881 for the South Asian population in gnomAD v4.1.0 (the lower threshold of the 95% CI of 184/86258 exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold of 0.001 for BS1, and therefore meets this criterion (BS1). While this variant is located in a splice region (+7/-21) (BP7 not met), the SpliceAI score is 0.03, which is less than the LGMD VCEP threshold of 0.05 (BP4). This variant appears to have been reported in an individual undergoing genetic testing for muscular dystrophy, but only as a single hit (LOVD DYSF_001370). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BS1, BP4.
Eurofins Ntd Llc (ga)	RCV000275365	SCV000345746	uncertain significance	not provided	2016-09-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000260889	SCV000431802	uncertain significance	Miyoshi myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000316173	SCV000431803	uncertain significance	Limb-girdle muscular dystrophy, recessive	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081454	SCV000649672	benign	Qualitative or quantitative defects of dysferlin	2025-01-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001081454	SCV001297887	uncertain significance	Qualitative or quantitative defects of dysferlin	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Natera, Inc.	RCV001272839	SCV001455231	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-24	no assertion criteria provided	clinical testing