ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8030A>G (p.Tyr2677Cys) (rs28942103)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545206 SCV000622797 uncertain significance Ataxia-telangiectasia syndrome 2018-12-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 2677 of the ATM protein (p.Tyr2677Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (rs28942103, ExAC no frequency). This variant has been reported in the literature in two individuals from a single family affected with a late-onset and mild form of ataxia-telangiectasia (PMID: 11826028). ClinVar contains an entry for this variant (Variation ID: 3045). Functional studies of this variant in transfected human cells have shown undetectable levels of ATM protein expression, and reduced colony survival upon exposure to ionizing radiation (PMID: 18634022). In addition, functional studies in cell lines from affected individuals that carry this variant along with a nonsense variant show reduced ATM protein expression, but only mild reduction of p53 phosphorylation (PMID: 11826028). In summary, this variant has been observed in affected individuals from a single family, and has been shown to affect protein function. However, without additional segregation data, this variant has been classified as a Variant of Uncertain Significance.
OMIM RCV000003186 SCV000023344 pathogenic Ataxia-telangiectasia variant 2002-01-01 no assertion criteria provided literature only

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