ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.132_143del (p.Gly45_Gly48del) (rs749094206)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478208 SCV000566941 uncertain significance not provided 2015-06-18 criteria provided, single submitter clinical testing This deletion of 12 nucleotides in CDK4 is denoted c.132_143del12 at the cDNA level and p.G45_G48del at the protein level. The normal sequence, with the bases that are deleted in braces, is GAGG[AGGTGGAGGAGG]CCTT. This in frame deletion results in the loss of 4 Glycine residues, 3 of which are conserved through mammals while the fourth is not conserved, and is located in the protein kinase domain and the Poly-Gly region (UniProt). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider CDK4 G45_G48del to be a variant of uncertain significance.
Ambry Genetics RCV000567506 SCV000669143 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing The c.132_143del12 variant (also known as p.G45_G48del) is located in coding exon 1 of the CDK4 gene. This variant results from an in-frame deletion of 12 nucleotides (AGGTGGAGGAGG) at positions 132 to 143. This results in the deletion of four glycine residues at codons 45 to 48. The deleted amino acid positions are somewhat well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000709233 SCV000838664 uncertain significance Cutaneous malignant melanoma 3 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001220185 SCV001392161 uncertain significance Hereditary melanoma 2019-08-19 criteria provided, single submitter clinical testing This variant, c.132_143del, results in the deletion of 4 amino acid(s) of the CDK4 protein (p.Gly45_Gly48del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 419254). Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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