Submissions for variant NM_032806.6(POMGNT2):c.71G>A (p.Arg24Gln)

gnomAD frequency: 0.00026  dbSNP: rs139245562

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000500278	SCV000596525	uncertain significance	not specified	2016-07-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000538687	SCV000652793	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	2022-08-23	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 24 of the POMGNT2 protein (p.Arg24Gln). This variant is present in population databases (rs139245562, gnomAD 0.08%). 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: 436370). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
GeneDx	RCV001571753	SCV001796281	uncertain significance	not provided	2023-06-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Athena Diagnostics	RCV001571753	SCV002817204	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing	This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Ambry Genetics	RCV003258835	SCV003976897	uncertain significance	Inborn genetic diseases	2023-06-13	criteria provided, single submitter	clinical testing	The c.71G>A (p.R24Q) alteration is located in exon 2 (coding exon 1) of the POMGNT2 gene. This alteration results from a G to A substitution at nucleotide position 71, causing the arginine (R) at amino acid position 24 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004730963	SCV005340109	uncertain significance	POMGNT2-related disorder	2024-07-11	no assertion criteria provided	clinical testing	The POMGNT2 c.71G>A variant is predicted to result in the amino acid substitution p.Arg24Gln. This variant has been reported in the homozygous state in an acutely ill infant (eTable 2 in Maron et al 2023. PubMed ID: 37432431). This variant is reported in 0.071% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.