Submissions for variant NM_001130987.2(DYSF):c.951+3_951+4del

dbSNP: rs1573663867

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001005020	SCV001164585	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2018-12-03	criteria provided, single submitter	research	The heterozygous c.951+3_951+4delAT variant in DYSF was identified by our study in the compound heterozygous state, with a VUS, in two siblings with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies. This variant is located in the 5’ splice region. Computational tools do suggest an impact to splicing (destruction of a natural splice site and creation of an in-frame cryptic splice site) and another variant predicted to impact the same splicing site was reported pathogenic in ClinVar (Variation ID: 283267). However, this information is not predictive enough to determine pathogenicity. Loss of function of the DYSF gene is an established disease mechanism for autosomal recessive LGMD. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PVS1_Moderate, PP1 (Richards 2015).
CeGaT Center for Human Genetics Tuebingen	RCV001726413	SCV001962262	likely pathogenic	not provided	2021-08-01	criteria provided, single submitter	clinical testing