2-65069473-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015147.3(CEP68):​c.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000921 in 1,519,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

CEP68
NM_015147.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.357
Variant links:
Genes affected
CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016345471).
BP6
Variant 2-65069473-C-T is Benign according to our data. Variant chr2-65069473-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3832039.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP68NM_015147.3 linkc.29C>T p.Ala10Val missense_variant Exon 2 of 7 ENST00000377990.7 NP_055962.2 Q76N32-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP68ENST00000377990.7 linkc.29C>T p.Ala10Val missense_variant Exon 2 of 7 1 NM_015147.3 ENSP00000367229.2 Q76N32-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000164
AC:
3
AN:
182630
Hom.:
0
AF XY:
0.0000207
AC XY:
2
AN XY:
96518
show subpopulations
Gnomad AFR exome
AF:
0.0000653
Gnomad AMR exome
AF:
0.0000454
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000619
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000512
AC:
7
AN:
1367158
Hom.:
0
Cov.:
30
AF XY:
0.00000747
AC XY:
5
AN XY:
669594
show subpopulations
Gnomad4 AFR exome
AF:
0.0000656
Gnomad4 AMR exome
AF:
0.0000329
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000515
Gnomad4 SAS exome
AF:
0.0000140
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.39e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000833
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 16, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
3.4
DANN
Benign
0.82
DEOGEN2
Benign
0.0022
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.54
T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.016
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.83
N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.51
N;N
REVEL
Benign
0.0090
Sift
Benign
0.44
T;T
Sift4G
Benign
0.46
T;T
Polyphen
0.0
B;B
Vest4
0.041
MVP
0.14
MPC
0.045
ClinPred
0.0037
T
GERP RS
-6.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.041
gMVP
0.046

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368107291; hg19: chr2-65296607; API