Submissions for variant NM_000314.8(PTEN):c.802-12T>C

gnomAD frequency: 0.00015  dbSNP: rs587781129

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127651	SCV000171230	benign	not specified	2014-02-06	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.
Counsyl	RCV000410996	SCV000489513	likely benign	Cowden syndrome 1	2016-10-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001108875	SCV001266162	benign	PTEN hamartoma tumor syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV001190642	SCV001358193	likely benign	Hereditary cancer-predisposing syndrome	2019-11-05	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001190642	SCV002528260	benign	Hereditary cancer-predisposing syndrome	2020-11-09	criteria provided, single submitter	curation
Ambry Genetics	RCV001190642	SCV002675520	likely benign	Hereditary cancer-predisposing syndrome	2016-01-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Myriad Genetics, Inc.	RCV000410996	SCV004019920	likely benign	Cowden syndrome 1	2023-04-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
All of Us Research Program, National Institutes of Health	RCV001108875	SCV004822641	likely benign	PTEN hamartoma tumor syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001108875	SCV001552018	likely benign	PTEN hamartoma tumor syndrome		no assertion criteria provided	clinical testing	The PTEN c.802-12T>C variant was not identified in the literature nor was it identified in the following databases: Cosmic, MutDB, LOVD 3.0, or Zhejiang Colon Cancer Database. The variant was identified in the databases: dbSNP (ID: rs587781129) as "With Likely benign allele", and ClinVar/Clinvitae (2x, benign/likely benign). The variant was identified in control databases in 51 of 204652 chromosomes at a frequency of 0.0002 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). Of note, in the Ashkenazi Jewish population the variant was identified in 40 of 8652 chromosomes (freq. 0.005). The c.802-12T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Conversely, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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.