Submissions for variant NM_016247.4(IMPG2):c.1495C>A (p.Pro499Thr)

gnomAD frequency: 0.00041  dbSNP: rs143635399

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000332618	SCV000439566	uncertain significance	Retinitis pigmentosa	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069684	SCV001234871	uncertain significance	not provided	2022-08-21	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 499 of the IMPG2 protein (p.Pro499Thr). This variant is present in population databases (rs143635399, gnomAD 0.05%). 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: 342349). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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	RCV002523237	SCV003688151	uncertain significance	Inborn genetic diseases	2022-08-01	criteria provided, single submitter	clinical testing	The c.1495C>A (p.P499T) alteration is located in exon 12 (coding exon 12) of the IMPG2 gene. This alteration results from a C to A substitution at nucleotide position 1495, causing the proline (P) at amino acid position 499 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV001699330	SCV001919365	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001069684	SCV001966584	likely benign	not provided		no assertion criteria provided	clinical testing