Variant chr6-131950945-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001901.4(CCN2):c.114G>C(p.Glu38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000057 in 1,403,506 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CCN2
NM_001901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

CCN2 (HGNC:2500): (cellular communication network factor 2) The protein encoded by this gene is a mitogen that is secreted by vascular endothelial cells. The encoded protein plays a role in chondrocyte proliferation and differentiation, cell adhesion in many cell types, and is related to platelet-derived growth factor. Certain polymorphisms in this gene have been linked with a higher incidence of systemic sclerosis. [provided by RefSeq, Nov 2009]

CCN2 links:

LINC01013 (HGNC:48987): (long intergenic non-protein coding RNA 1013)

LINC01013 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.085299164).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN2	NM_001901.4 linkuse as main transcript	c.114G>C	p.Glu38Asp	missense_variant	2/5	ENST00000367976.4	NP_001892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCN2	ENST00000367976.4 linkuse as main transcript	c.114G>C	p.Glu38Asp	missense_variant	2/5	1	NM_001901.4	ENSP00000356954	P1	P29279-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151816

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1251690

Hom.:

Cov.:

AF XY:

0.00000489

AC XY:

AN XY:

613470

show subpopulations

Gnomad4 AFR exome

AF:

0.0000411

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:

0.00000489

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151816

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

May 13, 2024

The c.114G>C (p.E38D) alteration is located in exon 2 (coding exon 2) of the CTGF gene. This alteration results from a G to C substitution at nucleotide position 114, causing the glutamic acid (E) at amino acid position 38 to be replaced by an aspartic acid (D). 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

0.072

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.6

DANN

Benign

0.75

DEOGEN2

Benign

0.22

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.51

M_CAP

Benign

0.034

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

REVEL

Benign

0.055

Sift

Benign

0.20

Sift4G

Benign

0.43

Polyphen

0.022

Vest4

0.15

MutPred

0.34

Loss of glycosylation at P41 (P = 0.1758);

MVP

0.48

MPC

0.57

ClinPred

0.17

GERP RS

-9.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.17

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