Variant 10-96019715-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001349008.3(CC2D2B):c.3779T>G(p.Ile1260Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,592,708 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2B	NM_001349008.3 linkuse as main transcript	c.3779T>G	p.Ile1260Ser	missense_variant	32/35	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.3779T>G	p.Ile1260Ser	missense_variant	32/35		NM_001349008.3	ENSP00000496666.2		Q6DHV5-5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000134

AC:

AN:

231862

Hom.:

AF XY:

0.000159

AC XY:

AN XY:

126056

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:

0.00117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000687

AC:

AN:

1440516

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

715818

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:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000132

AC:

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

Jun 28, 2023

The c.671T>G (p.I224S) alteration is located in exon 9 (coding exon 7) of the CC2D2B gene. This alteration results from a T to G substitution at nucleotide position 671, causing the isoleucine (I) at amino acid position 224 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

.;T;T;T

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Uncertain

-0.021

MutationAssessor

Uncertain

2.6

.;.;M;M

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.9

.;.;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

.;.;D;D

Sift4G

Uncertain

0.0020

.;.;D;D

Vest4

0.77, 0.77

MutPred

0.78

.;.;Gain of disorder (P = 0.0401);Gain of disorder (P = 0.0401);

MVP

0.51

MPC

0.24

ClinPred

0.47

GERP RS

5.1

Varity_R

0.13

gMVP

0.90

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