ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7547T>G (p.Phe2516Cys)

gnomAD frequency: 0.00001  dbSNP: rs774312539
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567980 SCV000660753 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-25 criteria provided, single submitter clinical testing The p.F2516C variant (also known as c.7547T>G), located in coding exon 50 of the ATM gene, results from a T to G substitution at nucleotide position 7547. The phenylalanine at codon 2516 is replaced by cysteine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000567980 SCV000904733 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-04 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with cysteine at codon 2516 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. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 9/251152 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000810836 SCV000951072 uncertain significance Ataxia-telangiectasia syndrome 2021-11-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2516 of the ATM protein (p.Phe2516Cys). This variant is present in population databases (rs774312539, gnomAD 0.04%). 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: 479079). 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 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.
Natera, Inc. RCV000810836 SCV002080754 uncertain significance Ataxia-telangiectasia syndrome 2020-02-10 no assertion criteria provided clinical testing

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