rs2289178

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001194998.2(CEP152):c.2378G>T(p.Ser793Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,614,020 control chromosomes in the GnomAD database, including 1,283 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 122 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 1161 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 links:

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=0.001398623).

BP6

Variant 15-48762575-C-A is Benign according to our data. Variant chr15-48762575-C-A is described in ClinVar as [Benign]. Clinvar id is 136722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48762575-C-A is described in Lovd as [Benign]. Variant chr15-48762575-C-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.2378G>T	p.Ser793Ile	missense_variant	18/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.2378G>T	p.Ser793Ile	missense_variant	18/27	1	NM_001194998.2	A2	O94986-4
CEP152	ENST00000399334.7 linkuse as main transcript	c.2378G>T	p.Ser793Ile	missense_variant	18/26	1		P2	O94986-3
CEP152	ENST00000325747.9 linkuse as main transcript	c.2099G>T	p.Ser700Ile	missense_variant	17/25	1		A2	O94986-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1682

AN:

152148

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.00933

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0200

AC:

5001

AN:

249468

Hom.:

301

AF XY:

0.0172

AC XY:

2331

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.00245

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.00722

Gnomad FIN exome

AF:

0.00636

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.00874

AC:

12769

AN:

1461752

Hom.:

1161

Cov.:

AF XY:

0.00838

AC XY:

6094

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.0436

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.00749

Gnomad4 FIN exome

AF:

0.00607

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0111

AC:

1697

AN:

152268

Hom.:

122

Cov.:

AF XY:

0.0121

AC XY:

903

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.00934

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00545

Hom.:

Bravo

AF:

0.0127

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00293

AC:

ESP6500EA

AF:

0.000488

AC:

ExAC

AF:

0.0183

AC:

2213

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Microcephaly 9, primary, autosomal recessive

Benign:1

Benign, 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 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. -

Seckel syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.012

T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.060

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

0.89

P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.044

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.22

B;.;B

Vest4

0.12

MPC

0.18

ClinPred

0.0063

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over