Variant chr6-131950549-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001901.4(CCN2):c.290-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,612,122 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 11 hom., cov: 33)

Exomes 𝑓: 0.012 ( 127 hom. )

Consequence

CCN2
NM_001901.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001584

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.366

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-131950549-G-A is Benign according to our data. Variant chr6-131950549-G-A is described in ClinVar as [Benign]. Clinvar id is 770730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1270 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN2	NM_001901.4 linkuse as main transcript	c.290-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.290-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001901.4	ENSP00000356954	P1	P29279-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1272

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00837

AC:

2057

AN:

245636

Hom.:

AF XY:

0.00820

AC XY:

1095

AN XY:

133564

show subpopulations

Gnomad AFR exome

AF:

0.00276

Gnomad AMR exome

AF:

0.00641

Gnomad ASJ exome

AF:

0.00313

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00233

Gnomad FIN exome

AF:

0.00948

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0122

AC:

17752

AN:

1459800

Hom.:

127

Cov.:

AF XY:

0.0118

AC XY:

8597

AN XY:

725894

show subpopulations

Gnomad4 AFR exome

AF:

0.00236

Gnomad4 AMR exome

AF:

0.00664

Gnomad4 ASJ exome

AF:

0.00242

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.00971

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.00788

GnomAD4 genome

AF:

0.00834

AC:

1270

AN:

152322

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00778

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CCN2: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.030

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