rs2289179

Variant names:

• chr15-48782342-C-T
• rs2289179
• NM_001194998.2:c.1322-112G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001194998.2(CEP152):​c.1322-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 860,446 control chromosomes in the GnomAD database, including 17,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5733 hom., cov: 32)
  • Exomes 𝑓: 0.16 (11622 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.524
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-48782342-C-T is Benign according to our data. Variant chr15-48782342-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.1322-112G>A		intron_variant	Intron 10 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.1322-112G>A		intron_variant	Intron 10 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.1322-112G>A		intron_variant	Intron 10 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1043-112G>A		intron_variant	Intron 9 of 24	1		ENSP00000321000.5
CEP152	ENST00000560322.5	n.1322-112G>A		intron_variant	Intron 10 of 12	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35332 AN: 151954 Hom.: 5718 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.158 AC: 111688 AN: 708374 Hom.: 11622 AF XY: 0.154 AC XY: 57929 AN XY: 375710

African (AFR) AF: 0.453 AC: 8456 AN: 18680

American (AMR) AF: 0.229 AC: 8172 AN: 35760

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 1617 AN: 20314

East Asian (EAS) AF: 0.444 AC: 14561 AN: 32798

South Asian (SAS) AF: 0.134 AC: 8951 AN: 66916

European-Finnish (FIN) AF: 0.137 AC: 4960 AN: 36290

Middle Eastern (MID) AF: 0.132 AC: 467 AN: 3538

European-Non Finnish (NFE) AF: 0.128 AC: 58620 AN: 459130

Other (OTH) AF: 0.168 AC: 5884 AN: 34948

GnomAD4 genome AF: 0.233 AC: 35373 AN: 152072 Hom.: 5733 Cov.: 32 AF XY: 0.232 AC XY: 17252 AN XY: 74360

African (AFR) AF: 0.445 AC: 18426 AN: 41398

American (AMR) AF: 0.184 AC: 2812 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0819 AC: 284 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2448 AN: 5184

South Asian (SAS) AF: 0.152 AC: 733 AN: 4822

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8545 AN: 68008

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.188 Hom.: 681

Bravo AF: 0.252

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.90
CADD	Benign	0.59
DANN	Benign	0.30
PhyloP100		-0.52
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: rs2289179; hg19: chr15-49074539; COSMIC: COSV57857211; COSMIC: COSV57857211;