NM_001194998.2:c.2281-293A>G

Variant names:

• chr15-48762965-T-C
• rs10519188
• NM_001194998.2:c.2281-293A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001194998.2(CEP152):​c.2281-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,790 control chromosomes in the GnomAD database, including 2,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2033 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.286
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-48762965-T-C is Benign according to our data. Variant chr15-48762965-T-C is described in ClinVar as Benign. ClinVar VariationId is 1238498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.2281-293A>G		intron_variant	Intron 17 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.2281-293A>G		intron_variant	Intron 17 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.2281-293A>G		intron_variant	Intron 17 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.2002-293A>G		intron_variant	Intron 16 of 24	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23164 AN: 151670 Hom.: 2025 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.153 AC: 23167 AN: 151790 Hom.: 2033 Cov.: 32 AF XY: 0.154 AC XY: 11453 AN XY: 74186

African (AFR) AF: 0.196 AC: 8069 AN: 41188

American (AMR) AF: 0.122 AC: 1867 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1966 AN: 5152

South Asian (SAS) AF: 0.134 AC: 646 AN: 4818

European-Finnish (FIN) AF: 0.140 AC: 1478 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8386 AN: 67992

Other (OTH) AF: 0.137 AC: 290 AN: 2112

Alfa AF: 0.0434 Hom.: 49

Bravo AF: 0.158

Asia WGS AF: 0.219 AC: 759 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10519188; hg19: chr15-49055162;