ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2522A>C (p.Asp841Ala) (rs587781812)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163825 SCV000214411 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-26 criteria provided, single submitter clinical testing The p.D841A variant (also known as c.2522A>C), located in coding exon 16 of the ATM gene, results from an A to C substitution at nucleotide position 2522. The aspartic acid at codon 841 is replaced by alanine, an amino acid with dissimilar properties. This alteration was previously reported in one Indian woman diagnosed with breast cancer at 47 years, who also had a sister with a history of breast cancer (Mannan AU et al. J. Hum. Genet., 2016 Jun;61:515-22). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000205271 SCV000261914 likely benign Ataxia-telangiectasia syndrome 2020-11-25 criteria provided, single submitter clinical testing
GeneDx RCV000589287 SCV000566199 uncertain significance not provided 2020-02-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26689913, 26911350, 29470806)
Fulgent Genetics,Fulgent Genetics RCV000515444 SCV000611352 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163825 SCV000682062 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589287 SCV000694228 uncertain significance not provided 2016-09-30 criteria provided, single submitter clinical testing Variant summary: The ATM c.2522A>C (p.Asp841Ala) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant. This variant is not located in any known domain (InterPro). This variant was found in 31/121120 control chromosomes (1 homozygote), predominantly observed in the South Asian subpopulation at a frequency of 0.0018845 (31/16450). This frequency is about 1.9 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005), suggesting this is possibly a benign polymorphism found primarily in the populations of South Asian origin. This variant has also been reported in two patients with breast or ovarian cancer without strong evidence for pathogenicity (i.e. co-segregation). In addition, multiple clinical diagnostic laboratories have classified this variant as uncertain significance. Taken together, this variant is currently classified as Variant of Uncertain Significance Possibly Benign.
PreventionGenetics,PreventionGenetics RCV000589287 SCV000805520 likely benign not provided 2017-11-10 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000589287 SCV000840927 likely benign not provided 2018-10-29 criteria provided, single submitter clinical testing

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