Variant 10-96027250-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001349008.3(CC2D2B):c.3986G>A(p.Arg1329Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,394,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2B	NM_001349008.3 linkuse as main transcript	c.3986G>A	p.Arg1329Gln	missense_variant	34/35	ENST00000646931.3
ENTPD1-AS1	NR_038444.1 linkuse as main transcript	n.296+62016C>T		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.3986G>A	p.Arg1329Gln	missense_variant	34/35		NM_001349008.3	P1	Q6DHV5-5
ENTPD1-AS1	ENST00000669711.1 linkuse as main transcript	n.300+62016C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

151886

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

80412

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000282

Gnomad SAS exome

AF:

0.0000464

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000115

AC:

AN:

1394678

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

687666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000957

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000844

Gnomad4 SAS exome

AF:

0.0000769

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Mar 29, 2024

The c.878G>A (p.R293Q) alteration is located in exon 11 (coding exon 9) of the CC2D2B gene. This alteration results from a G to A substitution at nucleotide position 878, causing the arginine (R) at amino acid position 293 to be replaced by a glutamine (Q). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

.;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

0.23

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.6

.;D

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Vest4

0.93

MutPred

0.77

.;Loss of MoRF binding (P = 0.0412);

MVP

0.61

MPC

0.58

ClinPred

0.69

GERP RS

5.7

gMVP

0.57

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over