Submissions for variant NM_000051.4(ATM):c.8593A>G (p.Ile2865Val)

gnomAD frequency: 0.00001  dbSNP: rs786202223

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164939	SCV000215628	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-10	criteria provided, single submitter	clinical testing	The p.I2865V variant (also known as c.8593A>G), located in coding exon 58 of the ATM gene, results from an A to G substitution at nucleotide position 8593. The isoleucine at codon 2865 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV000588681	SCV000322070	uncertain significance	not provided	2023-03-06	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15279808, 23532176)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588681	SCV000694382	uncertain significance	not provided	2016-08-08	criteria provided, single submitter	clinical testing	Variant summary: The ATM c.8593A>G (p.Ile2865Val) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 119776 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae	RCV000628009	SCV000748896	uncertain significance	Ataxia-telangiectasia syndrome	2023-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2865 of the ATM protein (p.Ile2865Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pancreatic ductal adenocarcinoma (PMID: 35171259). ClinVar contains an entry for this variant (Variation ID: 185499). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health	RCV000164939	SCV001354845	uncertain significance	Hereditary cancer-predisposing syndrome	2019-03-13	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164939	SCV002529957	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-16	criteria provided, single submitter	curation
Baylor Genetics	RCV003462156	SCV004207090	uncertain significance	Familial cancer of breast	2023-10-02	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000628009	SCV002082647	uncertain significance	Ataxia-telangiectasia syndrome	2020-02-12	no assertion criteria provided	clinical testing