ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.9006C>T (p.Phe3002=) (rs540172506)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162612 SCV000213042 likely benign Hereditary cancer-predisposing syndrome 2015-05-26 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.
GeneDx RCV000418356 SCV000512187 benign not specified 2015-05-11 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.
Invitae RCV001079828 SCV000558396 benign Ataxia-telangiectasia syndrome 2020-12-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162612 SCV000682530 benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757011 SCV000885032 likely benign not provided 2017-07-21 criteria provided, single submitter clinical testing The c.9006C>T variant (rs540172506) does not alter the amino acid sequence of the ATM protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with ataxia telangiectasia in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.02 percent (identified on 79 out of 277,134 chromosomes including 1 homozygote) and has been reported to ClinVar (Variation ID: 183808). Based on these observations, the c.9006C>T variant is likely to be benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354402 SCV001549013 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Phe3002= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs540172506) as "With Uncertain significance, other allele" and in ClinVar (classified as benign by GeneDx and Color Genomics and classified as likely benign by Ambry Genetics and Invitae). The variant was identified in control databases in 79 of 277134 chromosomes (1 homozygous) at a frequency of 0.0003, 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: European Non-Finnish in 8 of 126614 chromosomes (freq: 0.00006) and South Asian in 71 of 30782 chromosomes (freq: 0.002), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, or Finnish populations. The p.Phe3002= 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. In addition, 4 of 4 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, 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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