chr6-131950832-G-A

Position:

• chr6-131950832-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000367976.4(CCN2):​c.227C>T​(p.Pro76Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,387,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CCN2 ENST00000367976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCN2	NM_001901.4	c.227C>T	p.Pro76Leu	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	c.227C>T	p.Pro76Leu	missense_variant	2/5	1	NM_001901.4	ENSP00000356954	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.0000187 AC: 26 AN: 1387102 Hom.: 0 Cov.: 64 AF XY: 0.0000234 AC XY: 16 AN XY: 684992

Gnomad4 AFR exome AF: 0.0000943

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: 0.0000203

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 35

Bravo AF: 0.0000151

ExAC AF: 0.0000568 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.227C>T (p.P76L) alteration is located in exon 2 (coding exon 2) of the CTGF gene. This alteration results from a C to T substitution at nucleotide position 227, causing the proline (P) at amino acid position 76 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.34
Sift	Benign	0.070	T
Sift4G	Benign	0.65	T
Polyphen		0.99	D
Vest4		0.41
MutPred		0.58		Loss of disorder (P = 0.0295);
MVP		0.83
MPC		1.4
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.34
gMVP		0.40

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

Other links and lift over

dbSNP: rs778832399; hg19: chr6-132271972;