ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.295A>G (p.Ser99Gly) (rs137882485)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115169 SCV000183799 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000115169 SCV000902647 likely benign Hereditary cancer-predisposing syndrome 2015-12-02 criteria provided, single submitter clinical testing
Counsyl RCV000196996 SCV000790963 uncertain significance Ataxia-telangiectasia syndrome 2017-04-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515313 SCV000611354 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000588846 SCV000149078 uncertain significance not provided 2018-05-09 criteria provided, single submitter clinical testing This variant is denoted ATM c.295A>G at the cDNA level, p.Ser99Gly (S99G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). This variant has been observed in at least one individual with breast cancer (Tavtigian 2009), at least one individual with B-cell chronic lymphocytic leukemia (L?hdesm?ki 2004), and at least one individual with advanced cancer, not otherwise specified (Mandelker 2017). ATM Ser99Gly was observed at an allele frequency of 0.38% (39/10,144) in individuals of Ashkenazi Jewish ancestry in large population cohorts (Lek 2016). ATM Ser99Gly is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether ATM Ser99Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000588846 SCV000694242 uncertain significance not provided 2016-11-18 criteria provided, single submitter clinical testing Variant summary: The ATM c.295A>G (p.Ser99Gly) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 22/121804 control chromosomes at a frequency of 0.0001806, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). This variant has been reported in affected individuals without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. This variant has not to our knowledge been evaluated for functional effect via in vitro/vivo studies. Taken together, this variant is classified as VUS until more information becomes available.
Invitae RCV000196996 SCV000254077 likely benign Ataxia-telangiectasia syndrome 2018-01-12 criteria provided, single submitter clinical testing
Mendelics RCV000196996 SCV000838467 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000115169 SCV000787857 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing

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