ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8120C>G (p.Ser2707Cys) (rs748016261)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000447583 SCV000660529 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000447583 SCV000537544 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-15 criteria provided, single submitter clinical testing
Counsyl RCV000204523 SCV000796997 uncertain significance Ataxia-telangiectasia syndrome 2018-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000509525 SCV000569245 uncertain significance not provided 2017-09-13 criteria provided, single submitter clinical testing This variant is denoted ATM c.8120C>G at the cDNA level, p.Ser2707Cys (S2707C) at the protein level, and results in the change of a Serine to a Cysteine (TCC>TGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ser2707Cys was observed at an allele frequency of 0.012% (1/8622 alleles) in individuals of East Asian Ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Ser2707Cys occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether ATM Ser2707Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GenomeConnect, ClinGen RCV000509525 SCV000606904 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000204523 SCV000260658 uncertain significance Ataxia-telangiectasia syndrome 2018-09-25 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 2707 of the ATM protein (p.Ser2707Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs748016261, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 220257). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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