Submissions for variant NM_000077.5(CDKN2A):c.150+6T>C

gnomAD frequency: 0.00001  dbSNP: rs1025333664

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000582181	SCV000689583	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-08	criteria provided, single submitter	clinical testing	This variant causes a T to C nucleotide substitution at the +6 position of intron 1 of the CDKN2A (p16INK4A) gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001050279	SCV001214378	uncertain significance	Familial melanoma	2024-11-20	criteria provided, single submitter	clinical testing	This sequence change falls in intron 1 of the CDKN2A (p16INK4a) gene. It does not directly change the encoded amino acid sequence of the CDKN2A (p16INK4a) protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. ClinVar contains an entry for this variant (Variation ID: 491565). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001709671	SCV001936600	benign	not provided	2015-08-21	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000582181	SCV002534310	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-23	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003900299	SCV004712766	likely benign	CDKN2A-related disorder	2023-08-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).