chr15-48803005-T-G

Variant names:

• chr15-48803005-T-G
• rs34912622
• NM_001194998.2:c.87+2558A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001194998.2(CEP152):​c.87+2558A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,322 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (526 hom., cov: 33)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0985 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.87+2558A>C		intron	N/A	NP_001181927.1
	CEP152	NM_014985.4		c.87+2558A>C		intron	N/A	NP_055800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.87+2558A>C		intron	N/A	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.87+2558A>C		intron	N/A	ENSP00000382271.3
	CEP152	ENST00000325747.9	TSL:1	c.87+2558A>C		intron	N/A	ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11555 AN: 152204 Hom.: 527 Cov.: 33

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0759 AC: 11561 AN: 152322 Hom.: 526 Cov.: 33 AF XY: 0.0726 AC XY: 5410 AN XY: 74474

African (AFR) AF: 0.0487 AC: 2023 AN: 41572

American (AMR) AF: 0.0901 AC: 1378 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0532 AC: 257 AN: 4830

European-Finnish (FIN) AF: 0.0292 AC: 310 AN: 10622

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6837 AN: 68022

Other (OTH) AF: 0.0992 AC: 210 AN: 2116

Alfa AF: 0.0433 Hom.: 44

Bravo AF: 0.0771

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.20
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: rs34912622; hg19: chr15-49095202;