15-48767414-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R690C) has been classified as Uncertain significance.

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

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

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.2068C>A	p.Arg690Ser	missense	Exon 16 of 27	NP_001181927.1	O94986-4
	CEP152	NM_014985.4		c.2068C>A	p.Arg690Ser	missense	Exon 16 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.2068C>A	p.Arg690Ser	missense	Exon 16 of 27	ENSP00000370337.2	O94986-4
	CEP152	ENST00000399334.7	TSL:1	c.2068C>A	p.Arg690Ser	missense	Exon 16 of 26	ENSP00000382271.3	O94986-3
	CEP152	ENST00000325747.9	TSL:1	c.1789C>A	p.Arg597Ser	missense	Exon 15 of 25	ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.8
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.29
Sift	Benign	0.048	D
Sift4G	Benign	0.46	T
Polyphen		0.99	D
Vest4		0.72
MutPred		0.20		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

Other links and lift over

dbSNP: rs587783419; hg19: chr15-49059611;