NM_001194998.2:c.87+27dupA

Variant names:

• chr15-48805535-C-CT
• rs372967874
• NM_001194998.2:c.87+27dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001194998.2(CEP152):​c.87+27dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,198,422 control chromosomes in the GnomAD database, including 2,446 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (2291 hom., cov: 26)
  • Exomes 𝑓: 0.13 (155 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-48805535-C-CT is Benign according to our data. Variant chr15-48805535-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1278089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 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.87+27dupA		intron	N/A	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.87+27dupA		intron	N/A	NP_055800.2	O94986-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.87+27dupA		intron	N/A	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.87+27dupA		intron	N/A	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.87+27dupA		intron	N/A	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 22454 AN: 111376 Hom.: 2287 Cov.: 26

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.164 AC: 16145 AN: 98152 AF XY: 0.160

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.0908

Gnomad EAS exome AF: 0.331

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.133 AC: 144730 AN: 1087034 Hom.: 155 Cov.: 24 AF XY: 0.132 AC XY: 71997 AN XY: 543514

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

African (AFR) AF: 0.144 AC: 3619 AN: 25092

American (AMR) AF: 0.186 AC: 5803 AN: 31124

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 1656 AN: 19244

East Asian (EAS) AF: 0.275 AC: 7992 AN: 29034

South Asian (SAS) AF: 0.177 AC: 11537 AN: 65028

European-Finnish (FIN) AF: 0.137 AC: 4431 AN: 32272

Middle Eastern (MID) AF: 0.0938 AC: 374 AN: 3986

European-Non Finnish (NFE) AF: 0.123 AC: 103229 AN: 836690

Other (OTH) AF: 0.137 AC: 6089 AN: 44564

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.202 AC: 22461 AN: 111388 Hom.: 2291 Cov.: 26 AF XY: 0.213 AC XY: 11508 AN XY: 54072

African (AFR) AF: 0.201 AC: 6645 AN: 33016

American (AMR) AF: 0.307 AC: 3464 AN: 11268

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 288 AN: 2210

East Asian (EAS) AF: 0.563 AC: 2354 AN: 4182

South Asian (SAS) AF: 0.318 AC: 1141 AN: 3590

European-Finnish (FIN) AF: 0.214 AC: 1400 AN: 6534

Middle Eastern (MID) AF: 0.129 AC: 27 AN: 210

European-Non Finnish (NFE) AF: 0.141 AC: 6791 AN: 48314

Other (OTH) AF: 0.214 AC: 316 AN: 1476

Alfa AF: 0.0369 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs372967874; hg19: chr15-49097732;