ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6200C>A (p.Ala2067Asp) (rs397514577)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166627 SCV000217431 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s),Good segregation with disease (lod 1.5-3 = 5-9 meioses)
Color RCV000166627 SCV000903208 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-07 criteria provided, single submitter clinical testing
Counsyl RCV000258124 SCV000800774 pathogenic Ataxia-telangiectasia syndrome 2017-06-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762825 SCV000893183 pathogenic Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000258124 SCV000328268 pathogenic Ataxia-telangiectasia syndrome 2016-10-27 no assertion criteria provided literature only
Invitae RCV000258124 SCV000547142 pathogenic Ataxia-telangiectasia syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 2067 of the ATM protein (p.Ala2067Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with ataxia-telangiectasia (A-T) in three families (PMID: 22345219) where all affected individuals were homozygous for this variant. This sequence change has also been observed in unrelated individuals with A-T (PMID: 9887333, 25914063, Invitae). ClinVar contains an entry for this variant (Variation ID: 39749). Experimental studies have shown that this missense change leads to diminished protein expression and reduced enzyme activity in cells derived from patients homozygous for this variant and in cell lines expressing protein harboring the p.Ala2067Asp variant (PMID: 25077176). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000032965 SCV000056740 pathogenic Ataxia-telangiectasia variant 2012-02-28 no assertion criteria provided literature only

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