ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.962A>G (p.Asn321Ser) (rs1555068398)

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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 RCV000561753 SCV000667831 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbSNP, ESP, 1000 Genomes),Insufficient or Conflicting Evidence,in silico models in agreement (benign)
Color RCV000561753 SCV000687884 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587548 SCV000694393 uncertain significance not provided 2016-05-20 criteria provided, single submitter clinical testing Variant summary: The ATM c.962A>G (p.Asn321Ser) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPs&GO and Mutation Taster not captured due to low reliability index and p-value, respectively). This variant was absent in 120780 control chromosomes, and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000698316 SCV000826976 uncertain significance Ataxia-telangiectasia syndrome 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 321 of the ATM protein (p.Asn321Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 482541). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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