ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8314G>A (p.Gly2772Arg)

gnomAD frequency: 0.00001  dbSNP: rs1064794239
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486226 SCV000568337 uncertain significance not provided 2020-02-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate no damaging effect: no impact on cell viability, sensitivity to ionizing radiation, or induction of ATM kinase activity (Scott 2002); This variant is associated with the following publications: (PMID: 15279808, 16652348, 11606401, 19781682, 11805335, 29678143, 29522266, 30197789, 31920950, 21787400)
Ambry Genetics RCV000565973 SCV000660644 likely benign Hereditary cancer-predisposing syndrome 2022-05-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000670258 SCV000795091 uncertain significance Ataxia-telangiectasia syndrome 2017-10-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000670258 SCV000952280 uncertain significance Ataxia-telangiectasia syndrome 2023-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2772 of the ATM protein (p.Gly2772Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 11606401, 19781682, 29522266, 29678143). ClinVar contains an entry for this variant (Variation ID: 420015). 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. Experimental studies have shown that this missense change does not substantially affect ATM function (PMID: 11805335, 15279808). 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 RCV000565973 SCV001341245 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-24 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 2772 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). A functional study reported that the variant protein was able to rescue kinase activity, sensitivity and chromosomal aberrations in response to DNA damage when transfected into ATM-deficient cells (PMID: 11805335). This variant has been observed in three individuals affected with breast cancer (PMID: 11606401, 29678143, 31871109) and in at least one unaffected control (PMID: 29678143). 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.
Athena Diagnostics RCV000486226 SCV001475574 uncertain significance not provided 2020-01-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568173 SCV005057068 uncertain significance Familial cancer of breast 2024-01-19 criteria provided, single submitter clinical testing
Department of Human Genetics, Hannover Medical School RCV004568173 SCV005088416 uncertain significance Familial cancer of breast 2024-07-24 criteria provided, single submitter clinical testing

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