Submissions for variant GRCh38/hg38 2p13.2(chr2:71643868-71644161)x0

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003327662	SCV004034196	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2023-08-24	criteria provided, single submitter	research	A homozygous deletion of exon 42 in DYSF (NM_001130987.2) was identified by exome sequencing in one individual with limb-girdle muscular dystrophy ([GRCh 38] chr2:71643868_71644161x0). These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This variant is a deletion of 1 exon and is not predicted to alter the protein reading-frame. It is unclear if this deletion will impact the protein. Loss of function of DYSF is an established disease mechanism in autosomal recessive limb-girdle muscular dystrophy (https://search.clinicalgenome.org/kb/gene-dosage). In summary, the clinical significance of the variant is uncertain. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.30 points, 3: 0 points, 4-5: 0.15 points; Total: 0.45 points; Riggs 2020 (PMID: 31690835).