ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8567T>A (p.Val2856Glu)

dbSNP: rs1060501649
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000456168 SCV000546988 uncertain significance Ataxia-telangiectasia syndrome 2016-07-31 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. 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, but these predictions have not been confirmed by published functional studies. This sequence change replaces valine with glutamic acid at codon 2856 of the ATM protein (p.Val2856Glu). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glutamic acid.
Color Diagnostics, LLC DBA Color Health RCV003584606 SCV004361914 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-01 criteria provided, single submitter clinical testing This missense variant replaces valine with glutamic acid at codon 2856 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large international case-control study, this variant was reported in 1/60466 breast cancer cases and absent in 53461 controls (PMID: 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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