rs2289181

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.161C>T(p.Ser54Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0233 in 1,613,918 control chromosomes in the GnomAD database, including 2,498 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S54S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.029 ( 269 hom., cov: 32)

Exomes 𝑓: 0.023 ( 2229 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.69

Publications

21 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=0.0014413595).

BP6

Variant 15-48797978-G-A is Benign according to our data. Variant chr15-48797978-G-A is described in ClinVar as Benign. ClinVar VariationId is 136719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.161C>T	p.Ser54Leu	missense	Exon 3 of 27	NP_001181927.1
	CEP152	NM_014985.4		c.161C>T	p.Ser54Leu	missense	Exon 3 of 26	NP_055800.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP152	ENST00000380950.7	TSL:1 MANE Select	c.161C>T	p.Ser54Leu	missense	Exon 3 of 27	ENSP00000370337.2
CEP152	ENST00000399334.7	TSL:1	c.161C>T	p.Ser54Leu	missense	Exon 3 of 26	ENSP00000382271.3
CEP152	ENST00000325747.9	TSL:1	c.161C>T	p.Ser54Leu	missense	Exon 3 of 25	ENSP00000321000.5

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4368

AN:

152138

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.00670

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.0340

GnomAD2 exomes

AF:

0.0591

AC:

14720

AN:

249202

AF XY:

0.0561

show subpopulations

Gnomad AFR exome

AF:

0.00989

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.00705

Gnomad NFE exome

AF:

0.00543

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0228

AC:

33286

AN:

1461662

Hom.:

2229

Cov.:

AF XY:

0.0249

AC XY:

18077

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.00854

AC:

286

AN:

33474

American (AMR)

AF:

0.185

AC:

8270

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

649

AN:

26128

East Asian (EAS)

AF:

0.151

AC:

5985

AN:

39696

South Asian (SAS)

AF:

0.122

AC:

10536

AN:

86238

European-Finnish (FIN)

AF:

0.00698

AC:

373

AN:

53404

Middle Eastern (MID)

AF:

0.0219

AC:

126

AN:

5760

European-Non Finnish (NFE)

AF:

0.00474

AC:

5268

AN:

1111902

Other (OTH)

AF:

0.0297

AC:

1793

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1960

3920

5880

7840

9800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.0287

AC:

4375

AN:

152256

Hom.:

269

Cov.:

AF XY:

0.0336

AC XY:

2499

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0107

AC:

445

AN:

41554

American (AMR)

AF:

0.124

AC:

1899

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.151

AC:

784

AN:

5176

South Asian (SAS)

AF:

0.137

AC:

661

AN:

4824

European-Finnish (FIN)

AF:

0.00670

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00512

AC:

348

AN:

68018

Other (OTH)

AF:

0.0407

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

193

386

578

771

964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0187

Hom.:

511

Bravo

AF:

0.0346

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.0101

AC:

ESP6500EA

AF:

0.00610

AC:

ExAC

AF:

0.0531

AC:

6419

Asia WGS

AF:

0.168

AC:

582

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00516

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Microcephaly 9, primary, autosomal recessive (1)

Seckel syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.18

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.075

MPC

0.072

ClinPred

0.034

GERP RS

3.7

Varity_R

0.11

gMVP

0.30

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over