ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.210-7_210-3del (rs587780544)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131492 SCV000186480 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting benign classification,Rarity in general population databases (dbsnp, esp, 1000 genomes),Conflicting evidence
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000409649 SCV000579248 uncertain significance Cowden syndrome 1 2017-05-26 no assertion criteria provided research
ClinGen PTEN Variant Curation Expert Panel RCV000203983 SCV000930129 benign PTEN hamartoma tumor syndrome 2019-03-05 reviewed by expert panel curation PTEN c.210-7_210-3delCTTTT (IVS3-7_IVS3-3delCTTTT) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). BS1: Allele frequency of 0.00136 (0.14%, 14/10,306 alleles) in the Ashkenazi Jewish subpopulation of the gnomAD cohort. (PMID 27535533) BS3: Intronic OR synonymous variant with RNA, mini-gene, or other splicing assay demonstrating no splicing impact. (PMID 28677221)
Color RCV000131492 SCV000902621 likely benign Hereditary cancer-predisposing syndrome 2015-11-13 criteria provided, single submitter clinical testing
Counsyl RCV000409649 SCV000487849 uncertain significance Cowden syndrome 1 2015-11-23 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000254681 SCV000709617 likely benign not specified 2017-06-28 criteria provided, single submitter clinical testing
GeneDx RCV000254681 SCV000222138 likely benign not specified 2017-06-02 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.
Genetic Services Laboratory, University of Chicago RCV000254681 SCV000596623 uncertain significance not specified 2016-01-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000203983 SCV000365737 uncertain significance PTEN hamartoma tumor syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588392 SCV000696532 likely benign not provided 2017-04-06 criteria provided, single submitter clinical testing Variant summary: c.210-7_210-3delCTTTT in PTEN gene is an intronic change that involves a deletion of 5 non-conserved nucleotides. 5/5 programs in Alamut predict that this variant does not affect the normal splicing pattern, which was confirmed by Brown et al (2000). Another study reports that c.210-7_210-3delCTTTT, in fact, results in alternative splicing as two aberrant migrating transcripts were noted on gel electrophoresis in addition to the expected length product (Huang, 2000). However, authors failed to provide translational consequences for these aberrant transcripts, thus it remains unclear whether alternative transcripts play role in oncogenesis. The variant is present in the control population dataset of ExAC at a frequency of 0.00025 (29/114320 chrs tested), predominantly in individuals of European descent (0.00038; 24/62374 chrs tested). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.0000156. The variant is present in a control population dataset of gnomAD at a frequency of 0.00028 (78/275204 chrs), further supporting benign outcome. The variant of interest has been reported in multiple affected individuals presented with LFS, CS, CRC, EnCa without strong evidence for causality (Brown, 2000; Sweet, 2005; Ring, 2016; Pearlman, 2016). In one JPS family, the variant failed to segregate with the disease (Huang, 2000). In several published reports the variant is cited as VUS, whereas some authors list it as polymorphism, unlikely to be associated with LFS (Black, 2005). Lastly, reputable databases/clinical laboratories provide discordant classifications for the variant of interest ranging from VUS to Likely Benign. Considering all, the variant was classified as Likely Benign.
Invitae RCV000203983 SCV000262183 likely benign PTEN hamartoma tumor syndrome 2017-12-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254681 SCV000602118 uncertain significance not specified 2016-03-23 criteria provided, single submitter clinical testing

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