NM_000891.3:c.-163_-162insTC

Variant names:

• chr17-70174877-G-GTC
• rs61077847
• NM_000891.3:c.-163_-162insTC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• short QT syndrome type 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000891.3. 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	NM_000891.3	MANE Select	c.-163_-162insTC		5_prime_UTR	Exon 2 of 2	NP_000882.1	P63252

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ2	ENST00000243457.4	TSL:1 MANE Select	c.-163_-162insTC		5_prime_UTR	Exon 2 of 2	ENSP00000243457.2	P63252
	KCNJ2	ENST00000535240.1	TSL:1	c.-163_-162insTC		5_prime_UTR	Exon 2 of 2	ENSP00000441848.1	P63252
	KCNJ2	ENST00000854891.1		c.-163_-162insTC		5_prime_UTR	Exon 3 of 3	ENSP00000524950.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3150 AN: 152162 Hom.: 116 Cov.: 32

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.: 24 Cov.: 6 AF XY: 0.00219 AC XY: 662 AN XY: 302602

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: 0 AN: 19086

East Asian (EAS) AF: 0.00 AC: 0 AN: 32028

South Asian (SAS) AF: 0.000149 AC: 9 AN: 60218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34376

Middle Eastern (MID) AF: 0.00248 AC: 6 AN: 2424

European-Non Finnish (NFE) AF: 0.000150 AC: 50 AN: 333910

Other (OTH) AF: 0.00576 AC: 177 AN: 30706

GnomAD4 genome AF: 0.0207 AC: 3157 AN: 152280 Hom.: 117 Cov.: 32 AF XY: 0.0197 AC XY: 1468 AN XY: 74462

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: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68024

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Andersen Tawil syndrome;C1865018:Short QT syndrome type 3;C3151431:Atrial fibrillation, familial, 9 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs61077847; hg19: chr17-68171018;