Submissions for variant NM_000075.4(CDK4):c.447A>G (p.Thr149=)

gnomAD frequency: 0.00690  dbSNP: rs2069501

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163324	SCV000213852	benign	Hereditary cancer-predisposing syndrome	2015-01-07	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083024	SCV000261081	benign	Familial melanoma	2025-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000253216	SCV000301906	benign	not specified		criteria provided, single submitter	clinical testing
Counsyl	RCV000412354	SCV000488604	benign	Melanoma, cutaneous malignant, susceptibility to, 3	2016-06-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586842	SCV000695317	benign	not provided	2016-01-25	criteria provided, single submitter	clinical testing	Variant summary: The c.447A>G in CDK4 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at an overall frequency of 0.23%, being most prevalent in individuals of African descent (2.5%), including several homozygotes. The observed frequency exceeds the maximum expected allele frequency for a pathogenic CDK4 variant of 0.002%, suggesting that it is a common polymorphism. The variant has been reported as Benign by reputable database/clinical laboratory without providing evidence to independently evaluate. Taken together, this variant has been classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000253216	SCV000889266	benign	not specified	2021-05-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000586842	SCV001892974	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000253216	SCV002068246	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000253216	SCV002550005	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000412354	SCV004017031	benign	Melanoma, cutaneous malignant, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000412354	SCV004020047	benign	Melanoma, cutaneous malignant, susceptibility to, 3	2023-03-07	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Breakthrough Genomics, Breakthrough Genomics	RCV000586842	SCV005228950	benign	not provided		criteria provided, single submitter	not provided