ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.253+2T>A

dbSNP: rs1224040268
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000546522 SCV000645562 pathogenic PTEN hamartoma tumor syndrome 2022-10-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in partial intron inclusion and introduces a premature termination codon (PMID: 11071384). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 468676). Disruption of this splice site has been observed in individual(s) with juvenile polyposis syndrome and breast cancer and Cowden disease (PMID: 9259288, 17873119, 26681312). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the PTEN gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.
Fulgent Genetics, Fulgent Genetics RCV000763219 SCV000893846 pathogenic Macrocephaly-autism syndrome; Familial meningioma; Malignant tumor of prostate; VACTERL with hydrocephalus; Glioma susceptibility 2; PTEN hamartoma tumor syndrome; Cowden syndrome 1 2018-10-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004722901 SCV005339198 pathogenic PTEN-related disorder 2024-06-18 no assertion criteria provided clinical testing The PTEN c.253+2T>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge this variant has not been reported in literature; however, alternative splice variants in the same canonical splice donor site (c.253+1G>A, c.253+1G>C, c.253+1G>T, and c.253+2T>C) have been reported in individuals with PTEN-related disorders (Busch et al. 2013. PubMed ID: 23470840; Table S1, Susswein et al. 2016. PubMed ID: 26681312; Celebi et al. 2000. PubMed ID: 11071384; Human Gene Mutation Database, http://www.hgmd.cf.ac.uk/ac/index.php). This variant has not been reported in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice donor site in PTEN are expected to be pathogenic. This variant is interpreted as pathogenic.

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