Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001386795.1(DTNA):c.112G>C(p.Ala38Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38T) has been classified as Uncertain significance.
DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);.;Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);.;Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);Gain of glycosylation at A38 (P = 0.0384);