ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.157A>C (p.Lys53Gln) (rs876659078)

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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 RCV000215164 SCV000275107 uncertain significance Hereditary cancer-predisposing syndrome 2015-04-10 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000467915 SCV000546792 uncertain significance Ataxia-telangiectasia syndrome 2019-05-15 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 53 of the ATM protein (p.Lys53Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Color RCV000215164 SCV000681983 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001192390 SCV001360472 uncertain significance not specified 2019-07-10 criteria provided, single submitter clinical testing Variant summary: ATM c.157A>C (p.Lys53Gln) results in a conservative amino acid change located in the Telomere-length maintenance and DNA damage repair domain (IPR021668) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250966 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.157A>C in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported in an internal sample (BRCA2 c.5076delG, p.W1692fs*14). Three ClinVar submissions (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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