17-70174877-G-GTC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000891.3(KCNJ2):c.-163_-162insTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00655 in 714,988 control chromosomes in the GnomAD database, including 141 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 117 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 24 hom. )

Consequence

KCNJ2
NM_000891.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.87

Publications

0 publications found

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]

KCNJ2 Gene-Disease associations (from GenCC):

Andersen-Tawil syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
short QT syndrome type 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
short QT syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
long QT syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

KCNJ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 17-70174877-G-GTC is Benign according to our data. Variant chr17-70174877-G-GTC is described in ClinVar as [Likely_benign]. Clinvar id is 1273919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ2	NM_000891.3 link	c.-163_-162insTC		5_prime_UTR_variant	Exon 2 of 2	ENST00000243457.4	NP_000882.1	P63252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ2	ENST00000243457.4 link	c.-163_-162insTC		5_prime_UTR_variant	Exon 2 of 2	1	NM_000891.3	ENSP00000243457.2		P63252
KCNJ2	ENST00000535240.1 link	c.-163_-162insTC		5_prime_UTR_variant	Exon 2 of 2	1		ENSP00000441848.1		P63252

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3150

AN:

152162

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0715

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.00271

AC:

1523

AN:

562708

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

662

AN XY:

302602

show subpopulations

African (AFR)

AF:

0.0712

AC:

1133

AN:

15916

American (AMR)

AF:

0.00435

AC:

148

AN:

34044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19086

East Asian (EAS)

AF:

0.00

AC:

AN:

32028

South Asian (SAS)

AF:

0.000149

AC:

AN:

60218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34376

Middle Eastern (MID)

AF:

0.00248

AC:

AN:

2424

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

333910

Other (OTH)

AF:

0.00576

AC:

177

AN:

30706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0207

AC:

3157

AN:

152280

Hom.:

117

Cov.:

AF XY:

0.0197

AC XY:

1468

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0715

AC:

2970

AN:

41548

American (AMR)

AF:

0.00856

AC:

131

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68024

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

141

281

422

562

703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Andersen Tawil syndrome;C1865018:Short QT syndrome type 3;C3151431:Atrial fibrillation, familial, 9

Benign:1

Oct 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-70174877-G-GTC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over