Submissions for variant NM_000075.4(CDK4):c.684-10dup

gnomAD frequency: 0.00001  dbSNP: rs757684130

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000869433	SCV000570554	likely benign	not provided	2023-06-16	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080303	SCV001010860	likely benign	Familial melanoma	2025-01-30	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000869433	SCV001134096	likely benign	not provided	2019-04-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003401543	SCV004122359	likely benign	not specified	2023-10-30	criteria provided, single submitter	clinical testing	Variant summary: CDK4 c.684-10dupT duplicates a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation 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 8e-06 in 251286 control chromosomes (i.e., 2 heterozygotes; gnomAD v2.1 Exomes dataset). 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.684-10dupT in individuals affected with Cutaneous Malignant Melanoma and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Myriad Genetics, Inc.	RCV004787781	SCV005406084	likely benign	Melanoma, cutaneous malignant, susceptibility to, 3	2024-09-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
PreventionGenetics, part of Exact Sciences	RCV003942592	SCV004762545	likely benign	CDK4-related disorder	2019-03-08	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).