Submissions for variant NM_032806.6(POMGNT2):c.1258del (p.Ala420fs)

dbSNP: rs1575461722

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001009228	SCV001169048	likely pathogenic	not provided	2019-01-15	criteria provided, single submitter	clinical testing	The c.1258delG variant in the POMGNT2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1258delG variant causes a frameshift starting with codon Alanine 420, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 46 of the new reading frame, denoted p.Ala420LeufsX46. This frameshift variant in the C-terminus is predicted to result in protein truncation, as the last 161 amino acids are lost and replaced with 45 incorrect amino acids (Stenson et al., 2014). The c.1258delG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1258delG as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002549296	SCV003198271	pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	2022-05-12	criteria provided, single submitter	clinical testing	This variant disrupts a region of the POMGNT2 protein in which other variant(s) (p.Glu519*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 817989). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala420Leufs*46) in the POMGNT2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 161 amino acid(s) of the POMGNT2 protein.