ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8656G>A (p.Val2886Ile)

gnomAD frequency: 0.00001  dbSNP: rs1064795066
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483866 SCV000570509 uncertain significance not provided 2016-05-29 criteria provided, single submitter clinical testing This variant is denoted ATM c.8656G>A at the cDNA level, p.Val2886Ile (V2886I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Val2886Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. ATM Val2886Ile occurs at a position that is conserved across species and is located within the PI3-PI4 kinase domain and the p53 interaction domain (Tavtigian 2009, Stracker 2013, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Val2886Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000704042 SCV000832975 uncertain significance Ataxia-telangiectasia syndrome 2022-06-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2886 of the ATM protein (p.Val2886Ile). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 421335). 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 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.
Ambry Genetics RCV001018134 SCV001179326 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-19 criteria provided, single submitter clinical testing The p.V2886I variant (also known as c.8656G>A), located in coding exon 58 of the ATM gene, results from a G to A substitution at nucleotide position 8656. The valine at codon 2886 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003470570 SCV004211987 uncertain significance Familial cancer of breast 2023-05-07 criteria provided, single submitter clinical testing

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