Submissions for variant NM_000077.5(CDKN2A):c.106dup (p.Ala36fs)

dbSNP: rs398123152

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166566	SCV000217368	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-14	criteria provided, single submitter	clinical testing	The c.106dupG pathogenic mutation, located in coding exon 1 of the CDKN2A gene, results from a duplication of G at nucleotide position 106, causing a translational frameshift with a predicted alternate stop codon (p.A36Gfs*8). 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.
Eurofins Ntd Llc (ga)	RCV000078113	SCV000224143	pathogenic	not provided	2014-07-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000078113	SCV000566206	pathogenic	not provided	2015-04-06	criteria provided, single submitter	clinical testing	This duplication of one nucleotide in CDKN2A is denoted c.106dupG at the cDNA level and p.Ala36GlyfsX8 (A36GfsX8) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CGGGG[G]CGCT. The duplication causes a frameshift, which changes an Alanine to a Glycine at codon 36, and creates a premature stop codon at position 8 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000525168	SCV000637389	pathogenic	Familial melanoma	2021-08-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 92427). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala36Glyfs*8) 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).
Color Diagnostics, LLC DBA Color Health	RCV000166566	SCV004361314	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-06	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 1 of the CDKN2A (p16INK4A) gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with CDKN2A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDKN2A function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.