Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000542538 | SCV000652770 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 | 2022-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 40 of the POMGNT2 protein (p.Arg40Gln). This variant is present in population databases (rs146229269, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with POMGNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 473273). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV001764600 | SCV001998476 | uncertain significance | not provided | 2019-11-22 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Revvity Omics, |
RCV001764600 | SCV003811787 | uncertain significance | not provided | 2021-11-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005239200 | SCV005884683 | likely benign | not specified | 2024-12-09 | criteria provided, single submitter | clinical testing | Variant summary: POMGNT2 c.119G>A (p.Arg40Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 1612052 control chromosomes, predominantly at a frequency of 0.0015 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.34 fold of the estimated maximal expected allele frequency for a pathogenic variant in POMGNT2 causing Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 phenotype (0.0011). To our knowledge, no occurrence of c.119G>A in individuals affected with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 473273). Based on the evidence outlined above, the variant was classified as likely benign. |