ClinVar Miner

Submissions for variant NM_001184.4(ATR):c.2290A>G (p.Lys764Glu) (rs77208665)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000145296 SCV000192373 uncertain significance Seckel syndrome 1 2013-11-14 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000223960 SCV000281656 likely benign not provided 2016-01-20 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV000223960 SCV001001187 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000223960 SCV001154078 uncertain significance not provided 2018-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000145296 SCV001312159 benign Seckel syndrome 1 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000223960 SCV001550705 uncertain significance not provided no assertion criteria provided clinical testing The ATR p.Lys764Glu variant was identified in 1 of 100 proband chromosomes (frequency: 0.01) from individuals or families with breast cancer and was not identified in 72 control chromosomes from healthy individuals (Durocher_2006_17010193). In Wang et al., the variant was also identified in 1/48 breast cancer tumours (Wang_2008_PMID: 18281469). The variant was also identified in the following databases: dbSNP (ID: rs77208665) and was found in ClinVar (where it was reported as likely benign and a VUS for Seckel syndrome 1), Clinvitae, Cosmic (with a FATHMM prediction of Pathogenic (score=0.95)), MutDB and LOVD 3.0. The variant was identified in control databases in 902 of 281492 chromosomes (5 homozygous) at a frequency of 0.003204 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: Ashkenazi Jewish in 64 of 10326 chromosomes (freq: 0.006198), European (non-Finnish) in 630 of 128766 chromosomes (freq: 0.004893), other in 26 of 7180 chromosomes (freq: 0.003621), Latino in 89 of 35200 chromosomes (freq: 0.002528), European (Finnish) in 53 of 25088 chromosomes (freq: 0.002113), South Asian in 26 of 30084 chromosomes (freq: 0.000864) and African in 14 of 24956 chromosomes (freq: 0.000561); it was not observed in the East Asian populations. The p.Lys764 residue is not highly conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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