Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001130987.2(DYSF):c.1914C>G(p.Tyr638*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y638Y) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
DYSF (HGNC:3097): (dysferlin) The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-71553118-C-G is Pathogenic according to our data. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71553118-C-G is described in CliVar as Likely_pathogenic. Clinvar id is 3241383.Status of the report is criteria_provided_single_submitter, 1 stars.