15-48738216-T-C

Variant names:

• chr15-48738216-T-C
• rs766414465
• NM_001194998.2:c.*33A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001194998.2(CEP152):​c.*33A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000494 in 1,416,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: CEP152 NM_001194998.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.43
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.*33A>G		3_prime_UTR	Exon 27 of 27	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.*33A>G		3_prime_UTR	Exon 26 of 26	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.*33A>G		3_prime_UTR	Exon 27 of 27	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.*33A>G		3_prime_UTR	Exon 26 of 26	ENSP00000382271.3	O94986-3
	CEP152	ENST00000561245.1	TSL:2	n.142+3415A>G		intron	N/A	ENSP00000453591.1	H0YMG1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000503 AC: 1 AN: 198864 AF XY: 0.00000929

Gnomad AFR exome AF: 0.00

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: 0.00000494 AC: 7 AN: 1416832 Hom.: 0 Cov.: 30 AF XY: 0.00000571 AC XY: 4 AN XY: 700900

African (AFR) AF: 0.00 AC: 0 AN: 31474

American (AMR) AF: 0.00 AC: 0 AN: 39094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 37572

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1088006

Other (OTH) AF: 0.00 AC: 0 AN: 58420

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Microcephaly 9, primary, autosomal recessive (1)
-	1	-	Seckel syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.2
DANN	Benign	0.83
PhyloP100		1.4

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: rs766414465; hg19: chr15-49030413; COSMIC: COSV100358332; COSMIC: COSV100358332;