rs1555603936

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_000891.3(KCNJ2):​c.388A>G​(p.Thr130Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KCNJ2
NM_000891.3 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.37
Variant links:
Genes affected
KCNJ2 (HGNC:6263): (potassium inwardly rectifying channel subfamily J member 2) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Mutations in this gene have been associated with Andersen syndrome, which is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a disulfide_bond (size 32) in uniprot entity KCNJ2_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_000891.3
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KCNJ2. . Gene score misZ 2.7459 (greater than the threshold 3.09). Trascript score misZ 3.9347 (greater than threshold 3.09). GenCC has associacion of gene with long QT syndrome, short QT syndrome, Andersen-Tawil syndrome, familial atrial fibrillation, short QT syndrome type 3, catecholaminergic polymorphic ventricular tachycardia.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ2NM_000891.3 linkuse as main transcriptc.388A>G p.Thr130Ala missense_variant 2/2 ENST00000243457.4 NP_000882.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNJ2ENST00000243457.4 linkuse as main transcriptc.388A>G p.Thr130Ala missense_variant 2/21 NM_000891.3 ENSP00000243457 P1
KCNJ2ENST00000535240.1 linkuse as main transcriptc.388A>G p.Thr130Ala missense_variant 2/21 ENSP00000441848 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Andersen Tawil syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCenter For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And ColleaguesJul 20, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.20
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.73
D;D
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Uncertain
0.65
D
MutationAssessor
Uncertain
2.0
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.95
N;N
REVEL
Uncertain
0.53
Sift
Benign
0.33
T;T
Sift4G
Benign
0.25
T;T
Polyphen
0.37
B;B
Vest4
0.76
MutPred
0.55
Gain of catalytic residue at T130 (P = 0.0761);Gain of catalytic residue at T130 (P = 0.0761);
MVP
0.83
MPC
1.1
ClinPred
0.46
T
GERP RS
5.9
Varity_R
0.19
gMVP
0.96

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: rs1555603936; hg19: chr17-68171568; API