ClinVar Miner

Submissions for variant NM_001184.4(ATR):c.1904G>A (p.Arg635Gln)

gnomAD frequency: 0.00027  dbSNP: rs202162034
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001144959 SCV001305584 uncertain significance Seckel syndrome 1 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.
Invitae RCV001213729 SCV001385378 uncertain significance not provided 2024-01-25 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 635 of the ATR protein (p.Arg635Gln). This variant is present in population databases (rs202162034, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ATR-related conditions. ClinVar contains an entry for this variant (Variation ID: 900024). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001213729 SCV002048472 uncertain significance not provided 2021-10-25 criteria provided, single submitter clinical testing The ATR c.1904G>A; p.Arg635Gln variant (rs202162034), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 900024). This variant is included in the IBD exomes browser database with a mild average odds ratio of 1.30 for IBD. (https://ibd.broadinstitute.org/) without any segregation and functional data. This variant is found in the general population with an overall allele frequency of 0.02% (66/282122 alleles) in the Genome Aggregation Database. The arginine at codon 635 is weakly conserved but computational analyses predict that this variant is neutral (REVEL: 0.084). Due to limited information, the clinical significance of the p.Arg635Gln variant is uncertain at this time.
Genetic Services Laboratory, University of Chicago RCV001819849 SCV002071014 uncertain significance not specified 2021-09-23 criteria provided, single submitter clinical testing DNA sequence analysis of the ATR gene demonstrated a sequence change, c.1904G>A, in exon 9 that results in an amino acid change, p.Arg635Gln. This sequence change has been described in the gnomAD database with a frequency of 0.038% in the non-Finnish European subpopulation (dbSNP rs202162034). The p.Arg635Gln change affects a poorly conserved amino acid residue located in a domain of the ATR protein that is known to be functional. The p.Arg635Gln substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with ATR-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg635Gln change remains unknown at this time.
Ambry Genetics RCV002411649 SCV002722663 likely benign Inborn genetic diseases 2022-09-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity Omics RCV001213729 SCV003834502 uncertain significance not provided 2019-06-26 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003396772 SCV004111503 uncertain significance ATR-related condition 2022-12-07 criteria provided, single submitter clinical testing The ATR c.1904G>A variant is predicted to result in the amino acid substitution p.Arg635Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.038% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-142275399-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.