ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7502A>G (p.Asn2501Ser) (rs531617441)

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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 RCV000222504 SCV000276626 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Baylor Genetics RCV000233636 SCV000807599 uncertain significance Ataxia-telangiectasia syndrome 2017-09-01 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it in trans with a known deleterious mutation in a 10-year-old male with global delays, myopathy, epilepsy, generalize muscle weakness, and abnormal brain MRI. Heterozygotes are expected to be asymptomatic carriers.
Color RCV000222504 SCV000682418 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764945 SCV000896117 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000486420 SCV000569199 uncertain significance not provided 2019-01-17 criteria provided, single submitter clinical testing This variant is denoted ATM c.7502A>G at the cDNA level, p.Asn2501Ser (N2501S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. ATM Asn2501Ser was observed at an allele frequency of 0.13% (39/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). ATM Asn2501Ser is located in the FAT domain (Stracker 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Asn2501Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000233636 SCV000367067 uncertain significance Ataxia-telangiectasia syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000233636 SCV000283057 uncertain significance Ataxia-telangiectasia syndrome 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 2501 of the ATM protein (p.Asn2501Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs531617441, ExAC 0.1%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 232481). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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