Genetic Variant CEP152:c.87+26_87+27delAA (chr15-48805535-CTT-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_001194998.2(CEP152):c.87+26_87+27delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,220,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0026 ( 0 hom. )

Consequence

CEP152
NM_001194998.2 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0026 (2880/1109200) while in subpopulation AFR AF= 0.00491 (125/25456). AF 95% confidence interval is 0.00421. There are 0 homozygotes in gnomad4_exome. There are 1466 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000303

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:

0.000306

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000620

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00451

AC:

443

AN:

98152

Hom.:

AF XY:

0.00476

AC XY:

256

AN XY:

53738

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.00123

Gnomad SAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00541

Gnomad OTH exome

AF:

0.00485

GnomAD4 exome

AF:

0.00260

AC:

2880

AN:

1109200

Hom.:

AF XY:

0.00264

AC XY:

1466

AN XY:

555496

show subpopulations

Gnomad4 AFR exome

AF:

0.00491

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00437

Gnomad4 EAS exome

AF:

0.00191

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00552

Gnomad4 NFE exome

AF:

0.00246

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111476

Hom.:

Cov.:

AF XY:

0.0000555

AC XY:

AN XY:

54072

show subpopulations

Gnomad4 AFR

AF:

0.0000303

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000306

Gnomad4 NFE

AF:

0.0000620

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

15-48805535-CTTTTTTTTT-CTTTTTTT

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