19-1036169-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004368.4(CNN2):​c.430G>T​(p.Val144Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CNN2
NM_004368.4 missense

Scores

1
11
7

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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNN2NM_004368.4 linkc.430G>T p.Val144Phe missense_variant Exon 5 of 7 ENST00000263097.9 NP_004359.1 Q99439-1
CNN2NM_001303501.2 linkc.493G>T p.Val165Phe missense_variant Exon 5 of 7 NP_001290430.1 Q99439B4DUT8
CNN2NM_001303499.2 linkc.397G>T p.Val133Phe missense_variant Exon 5 of 7 NP_001290428.1 Q99439B4DDF4
CNN2NM_201277.3 linkc.391-247G>T 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>T p.Val144Phe missense_variant Exon 5 of 7 1 NM_004368.4 ENSP00000263097.2 Q99439-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249234
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460374
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
726404
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.61
D;.;T;.;.;.
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;.
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.48
T;T;T;T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.4
M;.;.;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.6
D;D;D;.;.;D
REVEL
Benign
0.26
Sift
Benign
0.11
T;D;D;.;.;T
Sift4G
Benign
0.26
T;T;T;T;T;T
Polyphen
0.78
P;P;D;.;.;.
Vest4
0.72
MutPred
0.33
.;.;Gain of methylation at K166 (P = 0.0797);.;.;.;
MVP
0.81
MPC
0.37
ClinPred
0.94
D
GERP RS
3.6
Varity_R
0.50
gMVP
0.83

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