ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.131_132insAA (p.Tyr44Ter)

dbSNP: rs730881673
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160403 SCV000210935 pathogenic Hereditary cancer-predisposing syndrome 2014-09-10 criteria provided, single submitter clinical testing The CDKN2A c.131_132insAA mutation has been reported previously in association with familial cutaneous malignant melanoma (Snoo et al., 2007). The insertion creates a premature Stop codon at position Tyrosine 44, denoted p.Tyr44Stop. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay. This variant has been observed to be inherited. The variant is found in CDKN2A panel(s).
Ambry Genetics RCV000160403 SCV000581512 pathogenic Hereditary cancer-predisposing syndrome 2019-02-04 criteria provided, single submitter clinical testing The c.131_132insAA pathogenic mutation (also known as p.Y44*), located in coding exon 1 of the CDKN2A gene, results from an insertion of two nucleotides at position 131. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. This mutation (also designated as "tyr44stop") has been reported in multiple melanoma cohorts (MacKie RM et al. J. Invest. Dermatol. 1998 Aug;111(2):269-72; de Snoo FA et al. J. Am. Acad. Dermatol. 2007 May;56(5):748-52; Potjer TP et al. J. Med. Genet. 2018 Oct;55(10):661-668). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001225200 SCV001397441 pathogenic Familial melanoma 2021-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr44*) in the CDKN2A (p16INK4a) gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKN2A (p16INK4a) are known to be pathogenic (PMID: 15146471, 16905682). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with melanoma (PMID: 9699728, 16234564, 17276542, 29661971). ClinVar contains an entry for this variant (Variation ID: 182409). For these reasons, this variant has been classified as Pathogenic.

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