Variant 10-96019311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001349008.3(CC2D2B):c.3739G>A(p.Val1247Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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:):

ENTPD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2309548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2B	NM_001349008.3 linkuse as main transcript	c.3739G>A	p.Val1247Ile	missense_variant	31/35	ENST00000646931.3	NP_001335937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2B	ENST00000646931.3 linkuse as main transcript	c.3739G>A	p.Val1247Ile	missense_variant	31/35		NM_001349008.3	ENSP00000496666.2		Q6DHV5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245770

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458748

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.631G>A (p.V211I) alteration is located in exon 8 (coding exon 6) of the CC2D2B gene. This alteration results from a G to A substitution at nucleotide position 631, causing the valine (V) at amino acid position 211 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.61

.;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

.;.;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.75

.;.;N;N

REVEL

Benign

0.074

Sift

Benign

0.23

.;.;T;T

Sift4G

Uncertain

0.025

.;.;D;D

Vest4

0.24, 0.23

MutPred

0.76

.;.;Gain of catalytic residue at V211 (P = 0.0732);Gain of catalytic residue at V211 (P = 0.0732);

MVP

0.17

MPC

0.091

ClinPred

0.11

GERP RS

4.3

Varity_R

0.023

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over