15-48767414-G-T

Variant names:

• chr15-48767414-G-T
• rs587783419
• NM_001194998.2:c.2068C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001194998.2(CEP152):​c.2068C>A​(p.Arg690Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.2068C>A	p.Arg690Ser	missense_variant	Exon 16 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.2068C>A	p.Arg690Ser	missense_variant	Exon 16 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.2068C>A	p.Arg690Ser	missense_variant	Exon 16 of 26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1789C>A	p.Arg597Ser	missense_variant	Exon 15 of 25	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.29
Sift	Benign	0.048	D;D;D
Sift4G	Benign	0.46	T;T;T
Polyphen		0.99	D;.;D
Vest4		0.72
MutPred		0.20		Loss of MoRF binding (P = 0.0278);Loss of MoRF binding (P = 0.0278);.;
MVP		0.89
MPC		0.41
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs587783419; hg19: chr15-49059611;