rs4135012
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001254.4(CDC6):c.883G>A(p.Asp295Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,613,948 control chromosomes in the GnomAD database, including 364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 30 hom., cov: 32)
Exomes 𝑓: 0.020 ( 334 hom. )
Consequence
CDC6
NM_001254.4 missense
NM_001254.4 missense
Scores
4
4
9
Clinical Significance
Conservation
PhyloP100: 8.43
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011202812).
BP6
?
Variant 17-40293996-G-A is Benign according to our data. Variant chr17-40293996-G-A is described in ClinVar as [Benign]. Clinvar id is 128638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-40293996-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0152 (2310/152318) while in subpopulation NFE AF= 0.023 (1565/68030). AF 95% confidence interval is 0.0221. There are 30 homozygotes in gnomad4. There are 1150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC6 | NM_001254.4 | c.883G>A | p.Asp295Asn | missense_variant | 6/12 | ENST00000209728.9 | |
CDC6 | XM_011525541.3 | c.883G>A | p.Asp295Asn | missense_variant | 6/13 | ||
CDC6 | XM_011525542.2 | c.883G>A | p.Asp295Asn | missense_variant | 6/13 | ||
CDC6 | XM_047437207.1 | c.883G>A | p.Asp295Asn | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC6 | ENST00000209728.9 | c.883G>A | p.Asp295Asn | missense_variant | 6/12 | 1 | NM_001254.4 | P1 | |
CDC6 | ENST00000649662.1 | c.883G>A | p.Asp295Asn | missense_variant | 6/12 | P1 | |||
CDC6 | ENST00000582402.1 | n.203-1360G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0152 AC: 2311AN: 152200Hom.: 30 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2311
AN:
152200
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0138 AC: 3471AN: 251476Hom.: 25 AF XY: 0.0138 AC XY: 1870AN XY: 135914
GnomAD3 exomes
AF:
AC:
3471
AN:
251476
Hom.:
AF XY:
AC XY:
1870
AN XY:
135914
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0203 AC: 29654AN: 1461630Hom.: 334 Cov.: 32 AF XY: 0.0199 AC XY: 14476AN XY: 727128
GnomAD4 exome
AF:
AC:
29654
AN:
1461630
Hom.:
Cov.:
32
AF XY:
AC XY:
14476
AN XY:
727128
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0152 AC: 2310AN: 152318Hom.: 30 Cov.: 32 AF XY: 0.0154 AC XY: 1150AN XY: 74494
GnomAD4 genome
?
AF:
AC:
2310
AN:
152318
Hom.:
Cov.:
32
AF XY:
AC XY:
1150
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
91
ALSPAC
AF:
AC:
96
ESP6500AA
AF:
AC:
21
ESP6500EA
AF:
AC:
182
ExAC
?
AF:
AC:
1586
Asia WGS
AF:
AC:
8
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 21, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CDC6: BS1, BS2 - |
Meier-Gorlin syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
T;.;.
Polyphen
P;P;P
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at