Submissions for variant NM_001184.4(ATR):c.992A>G (p.Asp331Gly)

gnomAD frequency: 0.00120  dbSNP: rs150008448

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000443991	SCV000516600	likely benign	not specified	2016-09-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000443991	SCV000593544	likely benign	not specified	2020-09-11	criteria provided, single submitter	clinical testing
Invitae	RCV000862591	SCV001003115	likely benign	not provided	2024-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001147813	SCV001308659	likely benign	Seckel syndrome 1	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000862591	SCV001477644	likely benign	not provided	2020-04-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002524842	SCV003677529	uncertain significance	Inborn genetic diseases	2021-04-20	criteria provided, single submitter	clinical testing	The c.992A>G (p.D331G) alteration is located in exon 4 (coding exon 4) of the ATR gene. This alteration results from a A to G substitution at nucleotide position 992, causing the aspartic acid (D) at amino acid position 331 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV001147813	SCV003801922	likely benign	Seckel syndrome 1	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126720	SCV003801923	likely benign	Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	2023-02-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000862591	SCV004148511	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	ATR: PP2, BP4, BS2
Center of Medical Genetics and Primary Health Care	RCV001005028	SCV000987287	uncertain significance	Familial cancer of breast	2020-04-08	no assertion criteria provided	research	ACMG Guidelines 2015 criteria PP4 Pathogenic Supporting: The patient has family history of breast cancer BS1 Benign Strong: GnomAD exomes allele frequency = 0.0014 > 0.000388 derived from the 207 clinically reported variants in gene ATR of which 6 PATH, 97 VUS and 104 BEN. BP1 Benign Supporting: 32 out of 32 non-VUS missense variants in gene ATR are BEN = 100.0% > threshold of 51.0%, and 104 out of 207 clinically reported variants in gene ATR are BEN = 50.2% > threshold of 24.0%. BP4 Benign Supporting: 10 benign predictions from DANN, DEOGEN2, EIGEN, FATHMM-MKL, M-CAP, MVP, MutationAssessor, MutationTaster, REVEL and SIFT vs no pathogenic predictions and the position is not conserved. Therefore, there is insufficient information and this variant was classified as a Variant of Unknown Significance.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000862591	SCV001800174	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000862591	SCV001973791	likely benign	not provided		no assertion criteria provided	clinical testing