2-65069593-G-A

Position:

• chr2-65069593-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015147.3(CEP68):​c.149G>A​(p.Gly50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2423738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.149G>A	p.Gly50Glu	missense_variant	2/7	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.149G>A	p.Gly50Glu	missense_variant	2/7	1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.149G>A (p.G50E) alteration is located in exon 2 (coding exon 1) of the CEP68 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	0.0087
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.16	T;T
Polyphen		1.0	D;D
Vest4		0.24
MutPred		0.34		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.53
MPC		0.30
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.17
gMVP		0.089

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-65296727;