17-70169388-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190

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

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
KCNJ2-AS1	NR_036534.1	n.15C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ2	ENST00000535240.1	c.-217+531G>A		intron_variant		1		P1
KCNJ2-AS1	ENST00000590966.2	n.17C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17995 AN: 151844 Hom.: 1106 Cov.: 32

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: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.119 AC: 18011 AN: 151952 Hom.: 1105 Cov.: 32 AF XY: 0.120 AC XY: 8904 AN XY: 74280

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.: 41

Bravo AF: 0.125

Asia WGS AF: 0.115 AC: 398 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
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

Other links and lift over

dbSNP: rs76457020; hg19: chr17-68165529;