rs7572857

chr2-65069664-G-A

Variant summary

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

The NM_015147.3(CEP68):c.220G>A(p.Gly74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,870 control chromosomes in the GnomAD database, including 22,225 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 0.13 (1638 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20587 hom.)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=0.003365755).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.220G>A	p.Gly74Ser	missense_variant	2/7	ENST00000377990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.220G>A	p.Gly74Ser	missense_variant	2/7	1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19280 AN: 152056 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.157 AC: 39374 AN: 250778 Hom.: 3621 AF XY: 0.166 AC XY: 22519 AN XY: 135706

Gnomad AFR exome AF: 0.0274

Gnomad AMR exome AF: 0.0964

Gnomad ASJ exome AF: 0.257

Gnomad EAS exome AF: 0.0946

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.162 AC: 237192 AN: 1461696 Hom.: 20587 Cov.: 33 AF XY: 0.165 AC XY: 120265 AN XY: 727158

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.0985

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.0822

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.127 AC: 19285 AN: 152174 Hom.: 1638 Cov.: 32 AF XY: 0.127 AC XY: 9459 AN XY: 74386

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.161

Alfa AF: 0.167 Hom.: 4750

Bravo AF: 0.119

TwinsUK AF: 0.146 AC: 543

ALSPAC AF: 0.159 AC: 613

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.176 AC: 1514

ExAC AF: 0.160 AC: 19410

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.082
Dann	Benign	0.68
DEOGEN2	Benign	0.00086	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.43	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.26	N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.62	N;N
REVEL	Benign	0.0080
Sift	Benign	0.72	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.014	B;B
Vest4		0.055
MPC		0.045
ClinPred		0.00045	T
GERP RS		-5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.054

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7572857; hg19: chr2-65296798; COSMIC: COSV53126109; COSMIC: COSV53126109;