rs12611491

Positions:

• chr2-65069523-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377990.7(CEP68):​c.79A>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,587,312 control chromosomes in the GnomAD database, including 1,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.022 (206 hom., cov: 32)
  • Exomes 𝑓: 0.016 (1481 hom.)
• Consequence: CEP68 ENST00000377990.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035800934).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.79A>G	p.Arg27Gly	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.79A>G	p.Arg27Gly	missense_variant	2/7	1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3356 AN: 152154 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.00905

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0416 AC: 9693 AN: 233006 Hom.: 738 AF XY: 0.0363 AC XY: 4580 AN XY: 126006

Gnomad AFR exome AF: 0.00808

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.0155

Gnomad EAS exome AF: 0.221

Gnomad SAS exome AF: 0.0146

Gnomad FIN exome AF: 0.0194

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0164 AC: 23545 AN: 1435040 Hom.: 1481 Cov.: 30 AF XY: 0.0159 AC XY: 11275 AN XY: 711082

Gnomad4 AFR exome AF: 0.00723

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.00506

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0220 AC: 3357 AN: 152272 Hom.: 206 Cov.: 32 AF XY: 0.0243 AC XY: 1809 AN XY: 74440

Gnomad4 AFR AF: 0.00902

Gnomad4 AMR AF: 0.0692

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.00532

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0159 Hom.: 179

Bravo AF: 0.0278

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.00640 AC: 55

ExAC AF: 0.0356 AC: 4323

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.18
DANN	Benign	0.75
DEOGEN2	Benign	0.0022	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.28	T;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.63	N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.014
Sift	Benign	0.15	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0	B;B
Vest4		0.029
MPC		0.052
ClinPred		0.00041	T
GERP RS		-3.7
Varity_R		0.13
gMVP		0.074

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: rs12611491; hg19: chr2-65296657; COSMIC: COSV53124852; COSMIC: COSV53124852;