Submissions for variant NM_000051.4(ATM):c.7871G>C (p.Cys2624Ser)

gnomAD frequency: 0.00001  dbSNP: rs759392666

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000696595	SCV000825160	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-16	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 2624 of the ATM protein (p.Cys2624Ser). This variant is present in population databases (rs759392666, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 574618). 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 tolerated. 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.
Mendelics	RCV000696595	SCV000838599	uncertain significance	Ataxia-telangiectasia syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001026894	SCV001189366	uncertain significance	Hereditary cancer-predisposing syndrome	2021-07-22	criteria provided, single submitter	clinical testing	The p.C2624S variant (also known as c.7871G>C), located in coding exon 52 of the ATM gene, results from a G to C substitution at nucleotide position 7871. The cysteine at codon 2624 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly 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	RCV001026894	SCV001349004	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-11	criteria provided, single submitter	clinical testing	This missense variant replaces cysteine with serine at codon 2624 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/250852 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798962	SCV002042946	uncertain significance	Breast and/or ovarian cancer	2020-07-22	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV003480779	SCV004226241	uncertain significance	not provided	2023-06-07	criteria provided, single submitter	clinical testing