Genetic Variant CEP152:c.87+22_87+27dupAAAAAA (chr15-48805535-C-CTTTTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001194998.2(CEP152):c.87+22_87+27dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,239,734 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CEP152
NM_001194998.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.181

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.87+22_87+27dupAAAAAA		intron_variant	Intron 2 of 26	ENST00000380950.7	NP_001181927.1	O94986-4Q3B7A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7 link	c.87+22_87+27dupAAAAAA		intron_variant	Intron 2 of 26	1	NM_001194998.2	ENSP00000370337.2		O94986-4

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000827

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000886

AC:

AN:

1128234

Hom.:

Cov.:

AF XY:

0.00000885

AC XY:

AN XY:

564890

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25918

American (AMR)

AF:

0.00

AC:

AN:

32310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19798

East Asian (EAS)

AF:

0.00

AC:

AN:

30708

South Asian (SAS)

AF:

0.00

AC:

AN:

68994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00000807

AC:

AN:

866950

Other (OTH)

AF:

0.0000649

AC:

AN:

46230

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.280

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000359

AC:

AN:

111500

Hom.:

Cov.:

AF XY:

0.0000370

AC XY:

AN XY:

54090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

11272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2210

East Asian (EAS)

AF:

0.00

AC:

AN:

4204

South Asian (SAS)

AF:

0.00

AC:

AN:

3620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0000827

AC:

AN:

48366

Other (OTH)

AF:

0.00

AC:

AN:

1464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Splicing

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

Publications

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15-48805535-CTTTTTTTTT-CTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over