Variant 19-1037767-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_004368.4(CNN2):c.797G>A(p.Arg266Gln) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.051 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNN2
NM_004368.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 19-1037767-G-A is Pathogenic according to our data. Variant chr19-1037767-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1696851.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNN2	NM_004368.4 linkuse as main transcript	c.797G>A	p.Arg266Gln	missense_variant	7/7	ENST00000263097.9	NP_004359.1
CNN2	NM_001303501.2 linkuse as main transcript	c.860G>A	p.Arg287Gln	missense_variant	7/7		NP_001290430.1
CNN2	NM_001303499.2 linkuse as main transcript	c.764G>A	p.Arg255Gln	missense_variant	7/7		NP_001290428.1
CNN2	NM_201277.3 linkuse as main transcript	c.680G>A	p.Arg227Gln	missense_variant	6/6		NP_958434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN2	ENST00000263097.9 linkuse as main transcript	c.797G>A	p.Arg266Gln	missense_variant	7/7	1	NM_004368.4	ENSP00000263097	P1	Q99439-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

4035

AN:

78982

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.0616

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.0304

Gnomad EAS

AF:

0.0429

Gnomad SAS

AF:

0.0430

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0236

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0000846

AC:

AN:

248214

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000109

AC:

156

AN:

1427600

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

110

AN XY:

706142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000324

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.000210

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000390

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.0000510

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.0511

AC:

4040

AN:

79012

Hom.:

Cov.:

AF XY:

0.0562

AC XY:

2146

AN XY:

38184

show subpopulations

Gnomad4 AFR

AF:

0.0735

Gnomad4 AMR

AF:

0.0392

Gnomad4 ASJ

AF:

0.0304

Gnomad4 EAS

AF:

0.0430

Gnomad4 SAS

AF:

0.0434

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0411

Gnomad4 OTH

AF:

0.0484

Alfa

AF:

0.204

Hom.:

ExAC

AF:

0.000222

AC:

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

0.97

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Pathogenic

0.62

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Uncertain

0.70

MutationAssessor

Benign

2.0

M;.;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.4

N;N;D;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.28

B;.;P;P

Vest4

0.50

MVP

0.92

MPC

0.14

ClinPred

0.15

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.62

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