rs201342438

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001194998.2(CEP152):c.2878T>C(p.Trp960Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00365 in 1,591,736 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 13 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:6B:4

Conservation

PhyloP100: 6.71

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048254102).

BP6

Variant 15-48756370-A-G is Benign according to our data. Variant chr15-48756370-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 95651.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00254 (386/152096) while in subpopulation NFE AF = 0.004 (272/67994). AF 95% confidence interval is 0.00361. There are 1 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

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.2878T>C	p.Trp960Arg	missense	Exon 20 of 27	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.2878T>C	p.Trp960Arg	missense	Exon 20 of 26	NP_055800.2	O94986-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP152	ENST00000380950.7	TSL:1 MANE Select	c.2878T>C	p.Trp960Arg	missense	Exon 20 of 27	ENSP00000370337.2	O94986-4
CEP152	ENST00000399334.7	TSL:1	c.2878T>C	p.Trp960Arg	missense	Exon 20 of 26	ENSP00000382271.3	O94986-3
CEP152	ENST00000325747.9	TSL:1	c.2599T>C	p.Trp867Arg	missense	Exon 19 of 25	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

387

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000756

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00253

AC:

591

AN:

233654

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.000394

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00628

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000867

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.00377

AC:

5427

AN:

1439640

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2629

AN XY:

713762

show subpopulations

African (AFR)

AF:

0.000652

AC:

AN:

32230

American (AMR)

AF:

0.00276

AC:

113

AN:

40972

Ashkenazi Jewish (ASJ)

AF:

0.00594

AC:

149

AN:

25100

East Asian (EAS)

AF:

0.00

AC:

AN:

39452

South Asian (SAS)

AF:

0.00117

AC:

AN:

81332

European-Finnish (FIN)

AF:

0.000910

AC:

AN:

52768

Middle Eastern (MID)

AF:

0.000356

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00433

AC:

4776

AN:

1102840

Other (OTH)

AF:

0.00376

AC:

223

AN:

59324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<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:

0.00254

AC:

386

AN:

152096

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000603

AC:

AN:

41470

American (AMR)

AF:

0.00353

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000756

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00400

AC:

272

AN:

67994

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00361

Hom.:

Bravo

AF:

0.00271

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00109

AC:

ESP6500EA

AF:

0.00427

AC:

ExAC

AF:

0.00243

AC:

294

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Microcephaly 9, primary, autosomal recessive (3)

CEP152-related disorder (1)

Seckel syndrome 5 (1)

Seckel syndrome 5;C3553886:Microcephaly 9, primary, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.048

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.6

PhyloP100

6.7

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-8.6

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.87

MutPred

0.44

Gain of solvent accessibility (P = 0.0171)

MVP

0.92

MPC

0.51

ClinPred

0.074

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.94

gMVP

0.61

Mutation Taster

=98/2

polymorphism

(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