ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.1321C>T (p.Gln441Ter)

dbSNP: rs1559587104
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000708935 SCV000838039 pathogenic BAP1-related tumor predisposition syndrome 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011008 SCV001171285 pathogenic Hereditary cancer-predisposing syndrome 2018-10-10 criteria provided, single submitter clinical testing The p.Q441* variant (also known as c.1321C>T), located in coding exon 13 of the BAP1 gene, results from a C to T substitution at nucleotide position 1321. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant has been reported in a family with melanocytic-BAP1-mutated atypical intradermal tumors, mesothelioma, renal cancer, and cutaneous melanoma (Haugh AM et al. JAMA Dermatol. 2017 Oct;153:999-1006; Garfield EM et al. J. Am. Acad. Dermatol. 2018 Sep;79:525-534). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000708935 SCV004293100 pathogenic BAP1-related tumor predisposition syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln441*) in the BAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAP1 are known to be pathogenic (PMID: 21874000, 23684012). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with melanocytic BAP1–mutated atypical intradermal tumors (MBAITs) (PMID: 28793149). ClinVar contains an entry for this variant (Variation ID: 584646). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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