ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5972A>G (p.Glu1991Gly)

dbSNP: rs866824608
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694743 SCV000823201 uncertain significance Ataxia-telangiectasia syndrome 2022-09-28 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 573153). This missense change has been observed in individual(s) with breast cancer (PMID: 31871109). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1991 of the ATM protein (p.Glu1991Gly).
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003344001 SCV004046892 uncertain significance Familial cancer of breast 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1991 of the ATM protein (p.Glu1991Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 31871109). ClinVar contains an entry for this variant (Variation ID: 573153). In-silico predictions show benign computationalverdict (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"). 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 RCV004025215 SCV005018174 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-21 criteria provided, single submitter clinical testing The p.E1991G variant (also known as c.5972A>G), located in coding exon 39 of the ATM gene, results from an A to G substitution at nucleotide position 5972. The glutamic acid at codon 1991 is replaced by glycine, an amino acid with similar properties. This variant has been reported in multiple individuals within a cohort of 3579 African individuals diagnosed with prostate cancer as well as a cohort of 196 African individuals diagnosed with breast cancer (Matejcic M et al. JCO Precis Oncol, 2020 Jan;4:32-43; Adedokun B et al. Cancer Epidemiol Biomarkers Prev, 2020 Feb;29:359-367). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000694743 SCV001457400 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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