rs759826252

Variant names:

• chr15-48805590-G-A
• rs759826252
• NM_001194998.2:c.60C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001194998.2(CEP152):​c.60C>T​(p.Asp20Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,587,162 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000025 (1 hom.)
• Consequence: CEP152 NM_001194998.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 2.18
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-48805590-G-A is Benign according to our data. Variant chr15-48805590-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210689.
• BP7: Synonymous conserved (PhyloP=2.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 2 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 2 of 27	1	NM_001194998.2	ENSP00000370337.2

Frequencies

GnomAD3 genomes AF: 0.0000221 AC: 3 AN: 135754 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000283 AC: 7 AN: 247090 AF XY: 0.0000298

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000248 AC: 36 AN: 1451408 Hom.: 1 Cov.: 36 AF XY: 0.0000360 AC XY: 26 AN XY: 722304

African (AFR) AF: 0.00 AC: 0 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38338

South Asian (SAS) AF: 0.000314 AC: 27 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1106872

Other (OTH) AF: 0.00 AC: 0 AN: 59652

GnomAD4 genome AF: 0.0000221 AC: 3 AN: 135754 Hom.: 0 Cov.: 30 AF XY: 0.0000155 AC XY: 1 AN XY: 64526

African (AFR) AF: 0.0000280 AC: 1 AN: 35776

American (AMR) AF: 0.0000799 AC: 1 AN: 12512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3376

East Asian (EAS) AF: 0.00 AC: 0 AN: 4692

South Asian (SAS) AF: 0.00 AC: 0 AN: 4422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000154 AC: 1 AN: 65140

Other (OTH) AF: 0.00 AC: 0 AN: 1834

Alfa AF: 0.0000355 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Jun 05, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.47
CADD	Benign	12
DANN	Benign	0.43
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs759826252; hg19: chr15-49097787;