Genetic Variant ENST00000535240.1:c.-217+531G>A (chr17-70169388-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000535240.1(KCNJ2):c.-217+531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,952 control chromosomes in the GnomAD database, including 1,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1105 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ2
ENST00000535240.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0190

Publications

3 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 links:

KCNJ2-AS1 (HGNC:43720): (KCNJ2 antisense RNA 1)

KCNJ2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-70169388-G-A is Benign according to our data. Variant chr17-70169388-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535240.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ2-AS1	NR_036534.1		n.15C>T		non_coding_transcript_exon	Exon 1 of 1
	KCNJ2	NM_000891.3	MANE Select	c.-530G>A		upstream_gene	N/A	NP_000882.1	P63252

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ2	ENST00000535240.1	TSL:1	c.-217+531G>A	intron	N/A	ENSP00000441848.1	P63252
KCNJ2	ENST00000854891.1		c.-217+531G>A	intron	N/A	ENSP00000524950.1
KCNJ2	ENST00000854892.1		c.-217+531G>A	intron	N/A	ENSP00000524951.1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

17995

AN:

151844

Hom.:

1106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0890

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.0926

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.126

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.119

AC:

18011

AN:

151952

Hom.:

1105

Cov.:

AF XY:

0.120

AC XY:

8904

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.105

AC:

4352

AN:

41500

American (AMR)

AF:

0.183

AC:

2793

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3468

East Asian (EAS)

AF:

0.0893

AC:

453

AN:

5072

South Asian (SAS)

AF:

0.178

AC:

862

AN:

4830

European-Finnish (FIN)

AF:

0.0926

AC:

980

AN:

10584

Middle Eastern (MID)

AF:

0.113

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.114

AC:

7738

AN:

67916

Other (OTH)

AF:

0.124

AC:

262

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

800

1600

2400

3200

4000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0439

Hom.:

Bravo

AF:

0.125

Asia WGS

AF:

0.115

AC:

398

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

-0.019

PromoterAI

-0.27

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over