Submissions for variant NM_000075.4(CDK4):c.219-7T>C

gnomAD frequency: 0.00001  dbSNP: rs543798269

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781219	SCV000919118	uncertain significance	not specified	2018-08-27	criteria provided, single submitter	clinical testing	Variant summary: CDK4 c.219-7T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 246128 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.219-7T>C in individuals affected with Cutaneous Malignant Melanoma and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001504802	SCV001709688	likely benign	Familial melanoma	2024-07-26	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004789179	SCV005404144	likely benign	Melanoma, cutaneous malignant, susceptibility to, 3	2024-09-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.