17-40289553-TCTC-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001254.4(CDC6):c.137_139delCTC(p.Pro46del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001254.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDC6 | NM_001254.4 | c.137_139delCTC | p.Pro46del | disruptive_inframe_deletion | Exon 2 of 12 | ENST00000209728.9 | NP_001245.1 | |
CDC6 | XM_011525541.3 | c.137_139delCTC | p.Pro46del | disruptive_inframe_deletion | Exon 2 of 13 | XP_011523843.1 | ||
CDC6 | XM_011525542.2 | c.137_139delCTC | p.Pro46del | disruptive_inframe_deletion | Exon 2 of 13 | XP_011523844.1 | ||
CDC6 | XM_047437207.1 | c.137_139delCTC | p.Pro46del | disruptive_inframe_deletion | Exon 2 of 12 | XP_047293163.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152100Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251470Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135910
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461856Hom.: 0 AF XY: 0.0000495 AC XY: 36AN XY: 727228
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74422
ClinVar
Submissions by phenotype
Meier-Gorlin syndrome Uncertain:1
- -
not provided Uncertain:1
This variant, c.137_139del, results in the deletion of 1 amino acid(s) of the CDC6 protein (p.Pro46del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs776043160, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CDC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 323053). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at