ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3154-4G>A (rs199543313)

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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 RCV000131267 SCV000186235 likely benign Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx RCV000211993 SCV000209596 benign not specified 2014-08-07 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 RCV001079697 SCV000252955 benign Ataxia-telangiectasia syndrome 2020-12-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131267 SCV000537432 likely benign Hereditary cancer-predisposing syndrome 2015-12-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588159 SCV000694250 uncertain significance not provided 2017-07-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000588159 SCV001148413 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV001079697 SCV001462133 uncertain significance Ataxia-telangiectasia syndrome 2020-01-10 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358310 SCV001554010 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM c.3154-4G>A variant was identified in 2 of 3100 proband chromosomes (frequency: 0.0006) from individuals or families with Lynch Syndrome and pancreatic cancer (Yurgelun 2015, Grant 2015). The variant was identified in dbSNP (rs199543313) as “with uncertain significance allele”, ClinVar (classified as likely benign by Invitae, Ambry Genetics and Color; as benign by GeneDx; and as uncertain significance by Integrated Genetics) and LOVD 3.0 (observed 1x). The variant was identified in control databases in 53 of 282,472 chromosomes at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 3 of 7206 chromosomes (freq: 0.0004), European in 36 of 128962 chromosomes (freq: 0.0003), Ashkenazi Jewish in 2 of 10,358 chromosomes (freq: 0.0002), Latino in 6 of 35,420 chromosomes (freq: 0.0002), South Asian in 4 of 30,602 chromosomes (freq: 0.0001), and African in 2 of 24,920 chromosomes (freq: 0.00008), while it was not observed in the East Asian or Finnish populations. The c.3154-4G>A variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions, nor does it affect positions -3 and -5 to -12, which are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, c.3154-4G>A is a non-highly conserved nucleotide and 4 out 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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