15-48805535-CTTTTTTT-CTTTTT

Position:

• chr15-48805535-CTTTTTTT-CTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_001194998.2(CEP152):​c.87+26_87+27del 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192

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]

ACMG classification

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/exons	MANE	UniProt
CEP152	NM_001194998.2	c.87+26_87+27del		intron_variant		ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.87+26_87+27del		intron_variant		1	NM_001194998.2	A2

Frequencies

GnomAD3 genomes AF: 0.0000538 AC: 6 AN: 111476 Hom.: 0 Cov.: 0

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.: 0 AF XY: 0.00476 AC XY: 256 AN XY: 53738

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.: 0 AF XY: 0.00264 AC XY: 1466 AN XY: 555496

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: 6 AN: 111476 Hom.: 0 Cov.: 0 AF XY: 0.0000555 AC XY: 3 AN XY: 54072

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs372967874; hg19: chr15-49097732;