Submissions for variant NM_001184.4(ATR):c.2776T>C (p.Phe926Leu)

gnomAD frequency: 0.00119  dbSNP: rs141783863

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000264411	SCV000441440	uncertain significance	Seckel syndrome 1	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.
Genetic Services Laboratory, University of Chicago	RCV000502214	SCV000593542	uncertain significance	not specified	2016-06-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000502214	SCV000730063	likely benign	not specified	2017-11-28	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000983891	SCV001131938	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000983891	SCV002506063	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing	The ATR c.2776T>C; p.Phe926Leu variant (rs141783863), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 343612). This variant is found in the Non-Finnish European population with an allele frequency of 0.19% (245/129028 alleles) in the Genome Aggregation Database. The phenylalanine at codon 926 is moderately conserved, but computation analyses are uncertain whether this variant is neutral or deleterious. (REVEL: 0.377). Due to limited information, the clinical significance of the p.Phe926Leu variant is uncertain at this time.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000983891	SCV001800805	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000983891	SCV001971093	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003969990	SCV004790509	likely benign	ATR-related disorder	2022-04-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).