Variant 19-1036205-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_004368.4(CNN2):c.466G>A(p.Asp156Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 150,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CNN2
NM_004368.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.61

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37273848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNN2	NM_004368.4 linkuse as main transcript	c.466G>A	p.Asp156Asn	missense_variant	5/7	ENST00000263097.9	NP_004359.1
CNN2	NM_001303501.2 linkuse as main transcript	c.529G>A	p.Asp177Asn	missense_variant	5/7		NP_001290430.1
CNN2	NM_001303499.2 linkuse as main transcript	c.433G>A	p.Asp145Asn	missense_variant	5/7		NP_001290428.1
CNN2	NM_201277.3 linkuse as main transcript	c.391-211G>A		intron_variant			NP_958434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN2	ENST00000263097.9 linkuse as main transcript	c.466G>A	p.Asp156Asn	missense_variant	5/7	1	NM_004368.4	ENSP00000263097	P1	Q99439-1

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.000487

GnomAD3 exomes

AF:

0.0000535

AC:

AN:

242812

Hom.:

AF XY:

0.0000534

AC XY:

AN XY:

131180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000902

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000819

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000864

AC:

1216

AN:

1406990

Hom.:

Cov.:

AF XY:

0.000883

AC XY:

614

AN XY:

695146

show subpopulations

Gnomad4 AFR exome

AF:

0.00235

Gnomad4 AMR exome

AF:

0.00979

Gnomad4 ASJ exome

AF:

0.00343

Gnomad4 EAS exome

AF:

0.0000770

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.000370

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.000794

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150566

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73418

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.000487

Alfa

AF:

0.0000663

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 04, 2024

The c.466G>A (p.D156N) alteration is located in exon 5 (coding exon 5) of the CNN2 gene. This alteration results from a G to A substitution at nucleotide position 466, causing the aspartic acid (D) at amino acid position 156 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;.;T;.;.;.

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

T;T;T;T;T;.

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.6

L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.3

N;N;N;.;.;N

REVEL

Benign

0.27

Sift

Uncertain

0.015

D;D;T;.;.;D

Sift4G

Uncertain

0.045

D;D;T;D;D;T

Polyphen

0.92

P;P;D;.;.;.

Vest4

0.35

MVP

0.71

MPC

0.097

ClinPred

0.43

GERP RS

4.8

Varity_R

0.26

gMVP

0.44

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