ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.735C>T (p.Val245=) (rs3218674)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162384 SCV000212697 benign Hereditary cancer-predisposing syndrome 2014-08-01 criteria provided, single submitter clinical testing This alteration is classified as 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.
Invitae RCV000204399 SCV000262457 benign Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000253651 SCV000301683 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000204399 SCV000367024 likely benign Ataxia-telangiectasia syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color Health, Inc RCV000162384 SCV000537370 benign Hereditary cancer-predisposing syndrome 2015-04-02 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000204399 SCV000745804 benign Ataxia-telangiectasia syndrome 2016-08-23 criteria provided, single submitter clinical testing
Counsyl RCV000204399 SCV000790971 likely benign Ataxia-telangiectasia syndrome 2017-04-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710681 SCV000840958 benign not provided 2017-09-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282153 SCV001159124 benign none provided 2020-06-17 criteria provided, single submitter clinical testing
GeneDx RCV000710681 SCV001894266 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 12810666)
True Health Diagnostics RCV000162384 SCV000787881 likely benign Hereditary cancer-predisposing syndrome 2018-02-20 no assertion criteria provided clinical testing
Natera, Inc. RCV000204399 SCV001454845 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358287 SCV001553979 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Val245= variant was identified in 44 of 3228 proband chromosomes (frequency: 0.01) from individuals or families with b-cell lymphoma tumours, chronic lymphocytic leukemia and hereditary breast and ovarian cancer and was present in 74 of 4368 control chromosomes (frequency: 0.007) from healthy individuals (Skowronska 2012, Concannon 2008, Gronbaek 2002, Heikkinen 2005, Mangone 2015, Petereit 2013, Tommiska 2006). The variant was identified in dbSNP (rs3218674) as “with likely benign, other allele, ClinVar (classified as benign by Invitae, Ambry Genetics, Color, PreventionGenetics and 2 other submitters and likely benign by True Health Diagnostics, Illumina and Counsyl) and LOVD 3.0 (observed 5x). The variant was identified in control databases in 3269 of 282,410 chromosomes (43 homozygous) at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Finnish in 1057 of 25,098 chromosomes (freq: 0.04), European in 1977 of 128,822 chromosomes (freq: 0.02), Other in 78 of 7206 chromosomes (freq: 0.01), Latino in 100 of 35,408 chromosomes (freq: 0.003), African in 45 of 24,960 chromosomes (freq: 0.002), South Asian in 10 of 30,610 chromosomes (freq: 0.0003), Ahkenazi Jewish in 2 of 10,360 chromosomes (freq: 0.0002), while the variant was not observed in the East Asian population. The p.Val245= 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 at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000253651 SCV001906377 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000253651 SCV001919583 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000253651 SCV001952863 benign not specified no assertion criteria provided clinical testing

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