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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ2-AS1	NR_036534.1 link	n.15C>T		non_coding_transcript_exon_variant	Exon 1 of 1
KCNJ2	NM_000891.3 link	c.-530G>A		upstream_gene_variant		ENST00000243457.4	NP_000882.1	P63252

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ2	ENST00000535240.1 link	c.-217+531G>A	intron_variant	Intron 1 of 1	1		ENSP00000441848.1	P63252
KCNJ2-AS1	ENST00000590966.2 link	n.17C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
KCNJ2	ENST00000243457.4 link	c.-530G>A	upstream_gene_variant		1	NM_000891.3	ENSP00000243457.2	P63252

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:

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.119

AC:

18011

AN:

151952

Hom.:

1105

Cov.:

AF XY:

0.120

AC XY:

8904

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0926

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0439

Hom.:

Bravo

AF:

0.125

Asia WGS

AF:

0.115

AC:

398

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: 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

-0.72

CADD

Benign

DANN

Benign

0.93

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over