ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3342G>A (p.Lys1114=) (rs138393322)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000988672 SCV000166100 benign Ataxia-telangiectasia syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000211997 SCV000167081 benign not specified 2013-12-11 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.
Ambry Genetics RCV000123738 SCV000213227 likely benign Hereditary cancer-predisposing syndrome 2014-07-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Health, Inc RCV000123738 SCV000682121 benign Hereditary cancer-predisposing syndrome 2015-02-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000211997 SCV000694258 likely benign not specified 2019-07-25 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000586815 SCV000805538 likely benign not provided 2016-10-03 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000586815 SCV000840933 benign not provided 2018-06-08 criteria provided, single submitter clinical testing
Mendelics RCV000988672 SCV001138485 likely benign Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000988672 SCV001260525 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356781 SCV001552042 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Lys1114= variant was identified in 1 of 244 proband chromosomes (frequency: 0.004) from individuals or families with breast cancer and was present in 1 of 298 control chromosomes (frequency: 0.003) from healthy individuals (Paglia 2010). The variant was also identified in dbSNP (ID: rs138393322) as With Likely benign allele, ClinVar (classified as benign by Invitae, GeneDx, Color Genomics; as likely benign by Ambry Genetics, IGLCA), Clinvitae, databases. The variant was not identified in GeneInsight-COGR, Cosmic, LOVD 3.0, databases. The variant was identified in control databases in 143 of 276622 chromosomes (1 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Other in 5 of 6460 chromosomes (freq: 0.001), Latino in 26 of 34366 chromosomes (freq: 0.001), European in 15 of 126286 chromosomes (freq: 0.0001), Ashkenazi Jewish in 97 of 10136 chromosomes (freq: 0.01), while the variant was not observed in the African, East Asian, Finnish, and South Asian populations. The p.Lys1114= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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