ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2932T>C (p.Ser978Pro) (rs139552233)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211991 SCV000149076 benign not specified 2017-05-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000119220 SCV000153964 benign Ataxia-telangiectasia syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115167 SCV000172932 benign Hereditary cancer-predisposing syndrome 2017-10-19 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;Co-occurence with mutation in same gene (phase unknown);Other data supporting benign classification
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000211991 SCV000343835 likely benign not specified 2016-07-22 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000584904 SCV000692731 likely benign not provided 2019-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000211991 SCV000694240 likely benign not specified 2020-07-22 criteria provided, single submitter clinical testing Variant summary: ATM c.2932T>C (p.Ser978Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00086 in 297768 control chromosomes (gnomAD and publication data). The variant was predominantly at a frequency of 0.0049 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Ataxia-Telangiectasia phenotype (0.004), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. This variant has been reported in multiple affected individuals with classical AT, classical Hodgkins lymphoma, B-NHL, BrC, CRC etc. Among them the one patient with classical AT also carried another ATM variant c.8395-8404del10, and no residual ATM activity was detected via western blot in this patient sample and only about 10% expressed ATM protein detected compared to WT (Carney_2012). However, the possibility of an undetected second variant causing AT in this patient cannot be ruled out. A study evaluating the Rate Ratio of asynchronous contralateral breast cancer associated with ATM gene mutation carrier status found a non-statistically significant risk of contralateral breast cancer for missense variants in the ATM gene (RR 1.2, 95% CI = 0.8 to 1.7) (Bernstein_2010). This low RR and a 95% CI overlapping 1.0 indicate very little confidence in the assertion of association with breast cancer. 11 ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (3x), likely benign (3x) and benign (5x). Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl RCV000119220 SCV000793508 likely benign Ataxia-telangiectasia syndrome 2017-08-17 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115167 SCV000821843 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000119220 SCV000838514 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000584904 SCV000840931 benign not provided 2019-07-18 criteria provided, single submitter clinical testing
Color RCV000115167 SCV000910564 benign Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119220 SCV001263808 uncertain significance Ataxia-telangiectasia syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.