17-70174878-A-AGAGTAGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000891.3(KCNJ2):c.-162_-161insGAGTAGT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 716,426 control chromosomes in the GnomAD database, including 142 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (117 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (25 hom.)
• Consequence: KCNJ2 NM_000891.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.471

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-70174878-A-AGAGTAGT is Benign according to our data. Variant chr17-70174878-A-AGAGTAGT is described in ClinVar as [Likely_benign]. Clinvar id is 1280715.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ2	NM_000891.3	c.-162_-161insGAGTAGT		5_prime_UTR_variant	2/2	ENST00000243457.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ2	ENST00000243457.4	c.-162_-161insGAGTAGT		5_prime_UTR_variant	2/2	1	NM_000891.3	P1
KCNJ2	ENST00000535240.1	c.-162_-161insGAGTAGT		5_prime_UTR_variant	2/2	1		P1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3148 AN: 152144 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: 1529 AN: 564164 Hom.: 25 Cov.: 6 AF XY: 0.00219 AC XY: 663 AN XY: 303374

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00575

GnomAD4 genome AF: 0.0207 AC: 3155 AN: 152262 Hom.: 117 Cov.: 32 AF XY: 0.0197 AC XY: 1467 AN XY: 74458

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0161

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Andersen Tawil syndrome;C1865018:Short QT syndrome type 3;C3151431:Atrial fibrillation, familial, 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 08, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58144126; hg19: chr17-68171019;