2-65069664-G-A

Variant names:

• chr2-65069664-G-A
• rs7572857
• NM_015147.3:c.220G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 43 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.220G>A	p.Gly74Ser	missense	Exon 2 of 7	NP_055962.2
	CEP68	NM_001319100.2		c.220G>A	p.Gly74Ser	missense	Exon 2 of 7	NP_001306029.1
	CEP68	NM_001410838.1		c.220G>A	p.Gly74Ser	missense	Exon 2 of 6	NP_001397767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.220G>A	p.Gly74Ser	missense	Exon 2 of 7	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.220G>A	p.Gly74Ser	missense	Exon 2 of 7	ENSP00000260569.4
	CEP68	ENST00000537589.1	TSL:1	n.74-1790G>A		intron	N/A

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

GnomAD2 exomes AF: 0.157 AC: 39374 AN: 250778 AF XY: 0.166

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 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

African (AFR) AF: 0.0271 AC: 908 AN: 33480

American (AMR) AF: 0.0985 AC: 4404 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6711 AN: 26136

East Asian (EAS) AF: 0.0822 AC: 3265 AN: 39700

South Asian (SAS) AF: 0.221 AC: 19068 AN: 86258

European-Finnish (FIN) AF: 0.166 AC: 8836 AN: 53244

Middle Eastern (MID) AF: 0.229 AC: 1318 AN: 5768

European-Non Finnish (NFE) AF: 0.164 AC: 182106 AN: 1111994

Other (OTH) AF: 0.175 AC: 10576 AN: 60392

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

African (AFR) AF: 0.0300 AC: 1247 AN: 41566

American (AMR) AF: 0.121 AC: 1854 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3466

East Asian (EAS) AF: 0.101 AC: 521 AN: 5174

South Asian (SAS) AF: 0.212 AC: 1024 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1719 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11544 AN: 67956

Other (OTH) AF: 0.161 AC: 339 AN: 2108

Alfa AF: 0.161 Hom.: 7977

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 v4.9

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
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.26	N
PhyloP100		-1.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.0080
Sift	Benign	0.72	T
Sift4G	Benign	0.74	T
Polyphen		0.014	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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7572857; hg19: chr2-65296798; COSMIC: COSV53126109; COSMIC: COSV53126109;