2-65069503-C-T

Variant names:

• chr2-65069503-C-T
• rs972966595
• NM_015147.3:c.59C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015147.3(CEP68):​c.59C>T​(p.Ser20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,415,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.503
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17295569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015147.3. 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
	CEP68	NM_015147.3	MANE Select	c.59C>T	p.Ser20Phe	missense	Exon 2 of 7	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.59C>T	p.Ser20Phe	missense	Exon 2 of 7	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.59C>T	p.Ser20Phe	missense	Exon 2 of 6	NP_001397767.1	A0A994J4E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.59C>T	p.Ser20Phe	missense	Exon 2 of 7	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.59C>T	p.Ser20Phe	missense	Exon 2 of 7	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000537589.1	TSL:1	n.74-1951C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000155 AC: 22 AN: 1415836 Hom.: 0 Cov.: 30 AF XY: 0.0000157 AC XY: 11 AN XY: 699518

African (AFR) AF: 0.00 AC: 0 AN: 32304

American (AMR) AF: 0.0000255 AC: 1 AN: 39210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22378

East Asian (EAS) AF: 0.00 AC: 0 AN: 39288

South Asian (SAS) AF: 0.00 AC: 0 AN: 79466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.0000175 AC: 19 AN: 1088026

Other (OTH) AF: 0.0000343 AC: 2 AN: 58250

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.50
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.024	D
Polyphen		0.98	D
Vest4		0.38
MutPred		0.20		Loss of phosphorylation at S20 (P = 0.0083)
MVP		0.36
MPC		0.23
ClinPred		0.81	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.13
Mutation Taster		=96/4	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: rs972966595; hg19: chr2-65296637; COSMIC: COSV106379364; COSMIC: COSV106379364;