dbSNP rs2144375995: KCNJ2:c.-216-7C>A (chr17-70174817-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000891.3(KCNJ2):c.-216-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 447,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

KCNJ2
NM_000891.3 splice_region, intron

Scores

Splicing: ADA: 0.0002102

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.352

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-70174817-C-A is Benign according to our data. Variant chr17-70174817-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1202336.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ2	NM_000891.3 link	c.-216-7C>A		splice_region_variant, intron_variant	Intron 1 of 1	ENST00000243457.4	NP_000882.1	P63252

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ2	ENST00000243457.4 link	c.-216-7C>A		splice_region_variant, intron_variant	Intron 1 of 1	1	NM_000891.3	ENSP00000243457.2		P63252
KCNJ2	ENST00000535240.1 link	c.-216-7C>A		splice_region_variant, intron_variant	Intron 1 of 1	1		ENSP00000441848.1		P63252

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000447

AC:

AN:

447790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

238724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12490

American (AMR)

AF:

0.00

AC:

AN:

20948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13832

East Asian (EAS)

AF:

0.00

AC:

AN:

29678

South Asian (SAS)

AF:

0.00

AC:

AN:

47068

European-Finnish (FIN)

AF:

0.0000366

AC:

AN:

27298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1940

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

268926

Other (OTH)

AF:

0.00

AC:

AN:

25610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 05, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.49

PhyloP100

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.030

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over