Submissions for variant NM_000077.5(CDKN2A):c.150+37G>C

gnomAD frequency: 0.00212  dbSNP: rs45456595

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000120548	SCV000149241	likely benign	not specified	2014-02-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204895	SCV000262426	benign	Familial melanoma	2024-10-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000411071	SCV000488766	uncertain significance	Melanoma-pancreatic cancer syndrome	2016-06-20	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000120548	SCV000538654	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in a family with melanoma, segregated in 2 individuals with atypical naevi and 1 with melanoma (Balogh 2012). MAF 0.3%.
Mendelics	RCV000411071	SCV001137780	likely benign	Melanoma-pancreatic cancer syndrome	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034475	SCV001155619	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	CDKN2A: BS1, BS2
Ambry Genetics	RCV001013481	SCV001174073	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-25	criteria provided, single submitter	clinical testing	The p.G63R variant (also known as c.187G>C), located in coding exon 1 of the CDKN2A gene, results from a G to C substitution at nucleotide position 187. The glycine at codon 63 is replaced by arginine, an amino acid with dissimilar properties. A 47 year old male patient with malignant melanoma at age 43, from an Italian melanoma family, was reported to have this variant; this individual did not have the pathogenic CDKN2A p.R24P mutation that was present in other family members (Della Torre G et al. Br. J. Cancer. 2001 Sep;85:836-44). This variant has been reported in individuals with single primary melanoma and with multiple primary melanomas (Goldstein AM et al. J. Med. Genet. 2008 May;45:284-9; Pastorino L et al. Pigment Cell Melanoma Res. 2008 Dec;21:700-9; Bruno W et al. J. Am. Acad. Dermatol. 2016 Feb;74:325-32). However, in other studies this variant has been reported in both melanoma cases controls (Harland M et al. Hered Cancer Clin Pract. 2014 Nov;12:20). Using a minigene assay to investigate mRNA splicing regulation, this variant had a differential splicing pattern from wild-type (Balogh K et al. Br. J. Dermatol. 2012 Jul;167:131-3). This variant has also been reported in studies of patients with pancreatic cancer (Ghiorzo P et al. J. Med. Genet. 2012 Mar;49:164-70; Grant RC et al. Gastroenterology. 2015 Mar;148:556-64). It was also identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS ONE. 2014 Apr;9:e94554); and it was detected as a secondary finding in 4 out of 567 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing (Johnston JJ et al. Am. J. Hum. Genet. 2012 Jul;91:97-108). This amino acid position is poorly conserved in available vertebrate species. Of note, this alteration is also designated as c.150+37G>C and IVS150+37G>C in the published literature. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034475	SCV002011089	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034475	SCV002047982	likely benign	not provided	2024-01-11	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001013481	SCV002534309	likely benign	Hereditary cancer-predisposing syndrome	2021-07-28	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120548	SCV002550364	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000411071	SCV004018566	benign	Melanoma-pancreatic cancer syndrome	2023-04-20	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing.
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034475	SCV000043254	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
ITMI	RCV000120548	SCV000084702	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV003891463	SCV000805819	likely benign	CDKN2A-related disorder	2020-02-07	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034475	SCV001744156	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000034475	SCV001905746	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000034475	SCV001958743	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000034475	SCV001970239	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034475	SCV002035301	likely benign	not provided		no assertion criteria provided	clinical testing