19-1036169-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004368.4(CNN2):​c.430G>C​(p.Val144Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V144I) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

CNN2
NM_004368.4 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31619865).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNN2NM_004368.4 linkc.430G>C p.Val144Leu missense_variant Exon 5 of 7 ENST00000263097.9 NP_004359.1 Q99439-1
CNN2NM_001303501.2 linkc.493G>C p.Val165Leu missense_variant Exon 5 of 7 NP_001290430.1 Q99439B4DUT8
CNN2NM_001303499.2 linkc.397G>C p.Val133Leu missense_variant Exon 5 of 7 NP_001290428.1 Q99439B4DDF4
CNN2NM_201277.3 linkc.391-247G>C intron_variant Intron 4 of 5 NP_958434.1 Q99439-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNN2ENST00000263097.9 linkc.430G>C p.Val144Leu missense_variant Exon 5 of 7 1 NM_004368.4 ENSP00000263097.2 Q99439-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Benign
0.0095
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;.;T;.;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;T;T;T;T;.
M_CAP
Benign
0.082
D
MetaRNN
Benign
0.32
T;T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.7
L;.;.;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-2.0
N;N;N;.;.;N
REVEL
Benign
0.17
Sift
Benign
0.064
T;T;T;.;.;T
Sift4G
Benign
0.26
T;T;T;T;T;T
Polyphen
0.0
B;B;B;.;.;.
Vest4
0.63
MutPred
0.29
.;.;Loss of methylation at K166 (P = 0.0354);.;.;.;
MVP
0.62
MPC
0.097
ClinPred
0.75
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.74

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.

Other links and lift over

dbSNP: rs201618086; hg19: chr19-1036168; API