ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.132C>T (p.Gly44=) (rs150651961)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000123045 SCV000840470 likely benign PTEN hamartoma tumor syndrome 2016-11-09 reviewed by expert panel curation PTEN c.132C>T (p.G44=) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BS1: Allele frequency of 0.167 (1.67%, 463/276,792 alleles) in the gnomAD cohort. (PMID 27535533) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (Internal laboratory contributor(s) SCV000212700.3) BP5: Variant found in multiple cases with alternate molecular basis for disease. (Internal laboratory contributor(s) SCV000212700.3) BP7: Variant is synonymous (silent), nucleotide is not conserved, and no splicing impact is predicted.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078606 SCV000110462 benign not specified 2013-10-21 criteria provided, single submitter clinical testing
Invitae RCV000123045 SCV000166340 benign PTEN hamartoma tumor syndrome 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162387 SCV000212700 likely benign Hereditary cancer-predisposing syndrome 2014-06-12 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV000123045 SCV000365736 likely benign PTEN hamartoma tumor syndrome 2018-06-28 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078606 SCV000602114 likely benign not specified 2017-01-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000078606 SCV000604970 benign not specified 2019-02-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512721 SCV000608560 likely benign not provided 2018-11-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162387 SCV000686277 likely benign Hereditary cancer-predisposing syndrome 2015-04-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000512721 SCV000696530 benign not provided 2016-01-25 criteria provided, single submitter clinical testing Variant summary: The c.132C>T variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. 3/5 programs in Alamut predict that this variant may create a novel 5' splicing donnor site. ESE finder predicts that this variant may affect ESE site of SRp55. However, these predictions are not confirmed by experimental studies. This variant is found in 190/121096 control chromosomes (1 homozygote) at a frequency of 0.001569. These alleles are unlikely from the PTEN pseudogene based on the sequence homology analysis and homozygous occurrences. This frequency is about 282 times of maximal expected frequency of a pathogenic allele (0.0000056), suggesting this variant is benign. In addition, multiple clinical laboratories classified this variant as benign/likely benign. Taken together, this variant was classified as benign.
PreventionGenetics,PreventionGenetics RCV000078606 SCV000806055 benign not specified 2016-05-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000512721 SCV000888588 benign not provided 2018-03-02 criteria provided, single submitter clinical testing
GeneDx RCV000512721 SCV001754035 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000078606 SCV000692003 likely benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000162387 SCV000788197 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357961 SCV001553575 benign Malignant tumor of breast no assertion criteria provided clinical testing The PTEN p.Gly44= variant was identified in 3 of 2724 proband chromosomes (frequency: 0.001) from individuals or families with prostate, breast cancer or Cowden syndrome and was not identified in 322 control chromosomes from healthy individuals (Bar-Shira 2006, Kurose 2002, Nizialek 2015). The variant was also identified in large population study by Momozawa (2018) in 6 of 14102 female chromosomes (frequency: 0.0004), and 4 in 22482 female control chromosomes (frequency: 0.0002) and 7 in 24980 male control chromosomes (frequency: 0.0003). The variant was also identified in dbSNP (ID: rs150651961) as "With other allele", ClinVar (classified as benign by Invitae, ARUP and four other submitters; as likely benign by eight submitters), LOVD 3.0 (7x as benign or likely benign). The variant was identified in control databases in 463 of 276792 chromosomes (3 homozygous) at a frequency of 0.002 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: African in 3 of 24028 chromosomes (freq: 0.0001), Other in 16 of 6452 chromosomes (freq: 0.003), Latino in 5 of 34378 chromosomes (freq: 0.0002), European in 319 of 126434 chromosomes (freq: 0.003), Ashkenazi Jewish in 33 of 10142 chromosomes (freq: 0.003), East Asian in 3 of 18856 chromosomes (freq: 0.0002), Finnish in 84 of 25724 chromosomes (freq: 0.003); it was not observed in the and South Asian populations. The p.Gly44= 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 outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000512721 SCV001740144 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000078606 SCV001918907 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000078606 SCV001958212 benign not specified no assertion criteria provided clinical testing

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