Variant rs1336459 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349008.3(CC2D2B):c.4310A>T(p.Gln1437Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,610,422 control chromosomes in the GnomAD database, including 2,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.039 ( 235 hom., cov: 32)

Exomes 𝑓: 0.046 ( 2313 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

CC2D2B (HGNC:31666): (coiled-coil and C2 domain containing 2B) Predicted to be involved in non-motile cilium assembly and protein localization to ciliary transition zone. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

CC2D2B links:

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ENTPD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021608174).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2B	NM_001349008.3 linkuse as main transcript	c.4310A>T	p.Gln1437Leu	missense_variant	35/35	ENST00000646931.3
ENTPD1-AS1	NR_038444.1 linkuse as main transcript	n.296+57262T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2B	ENST00000646931.3 linkuse as main transcript	c.4310A>T	p.Gln1437Leu	missense_variant	35/35		NM_001349008.3	P1	Q6DHV5-5
ENTPD1-AS1	ENST00000669711.1 linkuse as main transcript	n.300+57262T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5879

AN:

152152

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00919

Gnomad AMI

AF:

0.0958

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0556

AC:

13755

AN:

247324

Hom.:

931

AF XY:

0.0491

AC XY:

6591

AN XY:

134212

show subpopulations

Gnomad AFR exome

AF:

0.00915

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0371

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0459

AC:

66978

AN:

1458152

Hom.:

2313

Cov.:

AF XY:

0.0440

AC XY:

31922

AN XY:

725426

show subpopulations

Gnomad4 AFR exome

AF:

0.00692

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.0362

Gnomad4 NFE exome

AF:

0.0472

Gnomad4 OTH exome

AF:

0.0383

GnomAD4 genome

AF:

0.0387

AC:

5900

AN:

152270

Hom.:

235

Cov.:

AF XY:

0.0386

AC XY:

2877

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00917

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0408

Hom.:

116

Bravo

AF:

0.0461

TwinsUK

AF:

0.0458

AC:

170

ALSPAC

AF:

0.0485

AC:

187

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.0418

AC:

342

ExAC

AF:

0.0503

AC:

6071

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0406

EpiControl

AF:

0.0379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.43

.;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;.;L

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.6

.;.;.;D

REVEL

Benign

0.21

Sift

Uncertain

0.010

.;.;.;D

Sift4G

Uncertain

0.013

.;.;D;D

Vest4

0.13, 0.23

MPC

0.38

ClinPred

0.045

GERP RS

6.0

Varity_R

0.087

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over