Genetic Variant NM_015147.3:c.220G>A (chr2-65069664-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

43 publications found

Variant links:

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]

CEP68 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.220G>A	p.Gly74Ser	missense_variant	Exon 2 of 7	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19280

AN:

152056

Hom.:

1639

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.165

AC XY:

120265

AN XY:

727158

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12559

25119

37678

50238

62797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6282

12564

18846

25128

31410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19285

AN:

152174

Hom.:

1638

Cov.:

AF XY:

0.127

AC XY:

9459

AN XY:

74386

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11544

AN:

67956

Other (OTH)

AF:

0.161

AC:

339

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

846

1692

2538

3384

4230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.082

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.00086

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.26

N;N

PhyloP100

-1.0

PrimateAI

Benign

0.29

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

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over