rs193186571
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001254.4(CDC6):c.897G>A(p.Thr299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 0 hom. )
Consequence
CDC6
NM_001254.4 synonymous
NM_001254.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.540
Genes affected
CDC6 (HGNC:1744): (cell division cycle 6) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in cell nucleus during cell cyle G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during cell cyle is regulated through its phosphorylation by Cdks. Transcription of this protein was reported to be regulated in response to mitogenic signals through transcriptional control mechanism involving E2F proteins. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
Variant 17-40294010-G-A is Benign according to our data. Variant chr17-40294010-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434626.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.54 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC6 | NM_001254.4 | c.897G>A | p.Thr299= | synonymous_variant | 6/12 | ENST00000209728.9 | |
CDC6 | XM_011525541.3 | c.897G>A | p.Thr299= | synonymous_variant | 6/13 | ||
CDC6 | XM_011525542.2 | c.897G>A | p.Thr299= | synonymous_variant | 6/13 | ||
CDC6 | XM_047437207.1 | c.897G>A | p.Thr299= | synonymous_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC6 | ENST00000209728.9 | c.897G>A | p.Thr299= | synonymous_variant | 6/12 | 1 | NM_001254.4 | P1 | |
CDC6 | ENST00000649662.1 | c.897G>A | p.Thr299= | synonymous_variant | 6/12 | P1 | |||
CDC6 | ENST00000582402.1 | n.203-1346G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 63AN: 152198Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000350 AC: 88AN: 251478Hom.: 0 AF XY: 0.000316 AC XY: 43AN XY: 135918
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GnomAD4 exome AF: 0.000731 AC: 1068AN: 1461750Hom.: 0 Cov.: 32 AF XY: 0.000689 AC XY: 501AN XY: 727190
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GnomAD4 genome AF: 0.000414 AC: 63AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | CDC6: BP4, BP7 - |
Meier-Gorlin syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 13, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at