Submissions for variant NM_016247.4(IMPG2):c.2531G>A (p.Arg844Gln)

gnomAD frequency: 0.00003  dbSNP: rs139105788

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000360721	SCV000439558	uncertain significance	Retinitis pigmentosa	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Eurofins Ntd Llc (ga)	RCV000594708	SCV000701665	uncertain significance	not provided	2016-10-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000594708	SCV001399023	uncertain significance	not provided	2022-08-31	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 844 of the IMPG2 protein (p.Arg844Gln). This variant is present in population databases (rs139105788, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IMPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 342344). 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.
Ambry Genetics	RCV002520069	SCV003582076	uncertain significance	Inborn genetic diseases	2021-08-12	criteria provided, single submitter	clinical testing	The c.2531G>A (p.R844Q) alteration is located in exon 13 (coding exon 13) of the IMPG2 gene. This alteration results from a G to A substitution at nucleotide position 2531, causing the arginine (R) at amino acid position 844 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV000594708	SCV005189712	uncertain significance	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV001699468	SCV001923553	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000594708	SCV001971500	likely benign	not provided		no assertion criteria provided	clinical testing