ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8158G>C (p.Asp2720His)

dbSNP: rs876659942
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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 RCV000695980 SCV000824521 uncertain significance Ataxia-telangiectasia syndrome 2018-04-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 2720 of the ATM protein (p.Asp2720His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with a personal and/or family history of breast and/or ovarian cancer (PMID: 26534844). 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 and their clinical significance is uncertain. 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 RCV004678796 SCV005180299 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-28 criteria provided, single submitter clinical testing The p.D2720H variant (also known as c.8158G>C), located in coding exon 55 of the ATM gene, results from a G to C substitution at nucleotide position 8158. The aspartic acid at codon 2720 is replaced by histidine, an amino acid with similar properties. This alteration has been identified in high-risk non-BRCA1/2 family (Li J et al. J Med Genet, 2016 Jan;53:34-42). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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