15-48756508-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001194998.2(CEP152):c.2740C>G(p.Leu914Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,609,732 control chromosomes in the GnomAD database, including 5,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 370 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4733 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.829

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

microcephaly with or without short stature
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Seckel syndrome 5
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
microcephaly 9, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP152 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014411211).

BP6

Variant 15-48756508-G-C is Benign according to our data. Variant chr15-48756508-G-C is described in ClinVar as Benign. ClinVar VariationId is 136723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.2740C>G	p.Leu914Val	missense_variant	Exon 20 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CEP152	ENST00000380950.7 link	c.2740C>G	p.Leu914Val	missense_variant	Exon 20 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7 link	c.2740C>G	p.Leu914Val	missense_variant	Exon 20 of 26	1		ENSP00000382271.3
CEP152	ENST00000325747.9 link	c.2461C>G	p.Leu821Val	missense_variant	Exon 19 of 25	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes

AF:

0.0613

AC:

9308

AN:

151928

Hom.:

370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.0715

Gnomad SAS

AF:

0.0698

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0776

Gnomad OTH

AF:

0.0579

GnomAD2 exomes

AF:

0.0717

AC:

17658

AN:

246118

AF XY:

0.0744

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.0302

Gnomad ASJ exome

AF:

0.0630

Gnomad EAS exome

AF:

0.0754

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0699

GnomAD4 exome

AF:

0.0775

AC:

112989

AN:

1457686

Hom.:

4733

Cov.:

AF XY:

0.0777

AC XY:

56326

AN XY:

725316

show subpopulations

African (AFR)

AF:

0.0115

AC:

384

AN:

33474

American (AMR)

AF:

0.0318

AC:

1423

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0597

AC:

1559

AN:

26118

East Asian (EAS)

AF:

0.0681

AC:

2704

AN:

39686

South Asian (SAS)

AF:

0.0703

AC:

6061

AN:

86212

European-Finnish (FIN)

AF:

0.141

AC:

7023

AN:

49842

Middle Eastern (MID)

AF:

0.0531

AC:

306

AN:

5764

European-Non Finnish (NFE)

AF:

0.0804

AC:

89348

AN:

1111570

Other (OTH)

AF:

0.0693

AC:

4181

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

5265

10530

15796

21061

26326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3296

6592

9888

13184

16480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0612

AC:

9305

AN:

152046

Hom.:

370

Cov.:

AF XY:

0.0648

AC XY:

4818

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0154

AC:

639

AN:

41508

American (AMR)

AF:

0.0466

AC:

711

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3472

East Asian (EAS)

AF:

0.0715

AC:

369

AN:

5162

South Asian (SAS)

AF:

0.0698

AC:

336

AN:

4812

European-Finnish (FIN)

AF:

0.149

AC:

1573

AN:

10552

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0776

AC:

5278

AN:

67972

Other (OTH)

AF:

0.0578

AC:

122

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

439

878

1318

1757

2196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0594

Hom.:

115

Bravo

AF:

0.0513

TwinsUK

AF:

0.0747

AC:

277

ALSPAC

AF:

0.0781

AC:

301

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0741

AC:

603

ExAC

AF:

0.0724

AC:

8748

Asia WGS

AF:

0.0600

AC:

210

AN:

3478

EpiCase

AF:

0.0715

EpiControl

AF:

0.0706

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 18, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly 9, primary, autosomal recessive

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

PhyloP100

0.83

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0050

B;.;B

Vest4

0.040

MPC

0.073

ClinPred

0.0017

GERP RS

0.32

Varity_R

0.053

gMVP

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over