ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1955T>C (p.Phe652Ser)

gnomAD frequency: 0.00001  dbSNP: rs766259936
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240335 SCV001413269 uncertain significance Ataxia-telangiectasia syndrome 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 652 of the ATM protein (p.Phe652Ser). This variant is present in population databases (rs766259936, gnomAD 0.0009%). 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: 965804). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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.
GeneDx RCV001806076 SCV002050403 uncertain significance not provided 2021-06-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Ambry Genetics RCV002418823 SCV002718822 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-24 criteria provided, single submitter clinical testing The p.F652S variant (also known as c.1955T>C), located in coding exon 12 of the ATM gene, results from a T to C substitution at nucleotide position 1955. The phenylalanine at codon 652 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is well 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 RCV003469454 SCV004210039 uncertain significance Familial cancer of breast 2023-08-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001240335 SCV002083971 uncertain significance Ataxia-telangiectasia syndrome 2021-05-26 no assertion criteria provided clinical testing

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