Variant 19-1037757-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3PP5

The NM_004368.4(CNN2):c.787G>A(p.Gly263Ser) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.047 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00019 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CNN2
NM_004368.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.35

Variant links:

Genes affected

CNN2 (HGNC:2156): (calponin 2) The protein encoded by this gene, which can bind actin, calmodulin, troponin C, and tropomyosin, may function in the structural organization of actin filaments. The encoded protein could play a role in smooth muscle contraction and cell adhesion. Several pseudogenes of this gene have been identified, and are present on chromosomes 1, 2, 3, 6, 9, 11, 13, 15, 16, 21 and 22. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

CNN2 links:

CNN2 (HGNC:):

CNN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

PP5

Variant 19-1037757-G-A is Pathogenic according to our data. Variant chr19-1037757-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1696852.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNN2	NM_004368.4 linkuse as main transcript	c.787G>A	p.Gly263Ser	missense_variant	7/7	ENST00000263097.9	NP_004359.1	Q99439-1
CNN2	NM_001303501.2 linkuse as main transcript	c.850G>A	p.Gly284Ser	missense_variant	7/7		NP_001290430.1	Q99439B4DUT8
CNN2	NM_001303499.2 linkuse as main transcript	c.754G>A	p.Gly252Ser	missense_variant	7/7		NP_001290428.1	Q99439B4DDF4
CNN2	NM_201277.3 linkuse as main transcript	c.670G>A	p.Gly224Ser	missense_variant	6/6		NP_958434.1	Q99439-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN2	ENST00000263097.9 linkuse as main transcript	c.787G>A	p.Gly263Ser	missense_variant	7/7	1	NM_004368.4	ENSP00000263097.2		Q99439-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

3785

AN:

80904

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0689

Gnomad AMI

AF:

0.0602

Gnomad AMR

AF:

0.0385

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.0386

Gnomad FIN

AF:

0.0670

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.000133

AC:

AN:

247998

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000191

AC:

273

AN:

1430266

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

193

AN XY:

708098

show subpopulations

Gnomad4 AFR exome

AF:

0.000334

Gnomad4 AMR exome

AF:

0.0000461

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.000836

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.0000509

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.0468

AC:

3789

AN:

80924

Hom.:

Cov.:

AF XY:

0.0519

AC XY:

2040

AN XY:

39342

show subpopulations

Gnomad4 AFR

AF:

0.0688

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.0430

Gnomad4 SAS

AF:

0.0391

Gnomad4 FIN

AF:

0.0670

Gnomad4 NFE

AF:

0.0354

Gnomad4 OTH

AF:

0.0472

Alfa

AF:

0.356

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary artery atresia

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Henan Key Laboratory of Chronic Disease Management, Central China Fuwai Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital & Central China Branch of National Center for Cardiovascular Diseases

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.;.;T

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Pathogenic

0.78

MetaRNN

Pathogenic

0.77

D;D;D;D

MetaSVM

Pathogenic

0.99

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.038

D;D;D;D

Polyphen

0.99

D;.;D;D

Vest4

0.82

MVP

0.97

MPC

0.36

ClinPred

0.25

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.61

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