1-215081964-T-C

Variant names:

• chr1-215081964-T-C
• rs2363561
• ENST00000391895.6:c.35-4404T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017424.3(KCNK2):​c.35-4404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,864 control chromosomes in the GnomAD database, including 26,482 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26463 hom., cov: 30)
  • Exomes 𝑓: 0.63 (19 hom.)
• Consequence: KCNK2 NM_001017424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

Genes affected

KCNK2 (HGNC:6277): (potassium two pore domain channel subfamily K member 2) This gene encodes one of the members of the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential. The channel can be opened, however, by certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

LOC124904511 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK2	XM_011509524.3	c.-301T>C		5_prime_UTR_variant	Exon 1 of 7		XP_011507826.1
KCNK2	NM_001017424.3	c.35-4404T>C		intron_variant	Intron 1 of 6		NP_001017424.1
KCNK2	XM_017001249.2	c.5-4404T>C		intron_variant	Intron 2 of 7		XP_016856738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000391895.6	c.35-4404T>C		intron_variant	Intron 1 of 6	1		ENSP00000375765.2
KCNK2	ENST00000467031.5	n.35-4404T>C		intron_variant	Intron 1 of 5	1		ENSP00000420203.1
KCNK2	ENST00000478774.5	c.-144+103T>C		intron_variant	Intron 1 of 4	4		ENSP00000420569.1
KCNK2	ENST00000486921.5	n.35-4404T>C		intron_variant	Intron 1 of 6	5		ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88719 AN: 151644 Hom.: 26441 Cov.: 30

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.627 AC: 64 AN: 102 Hom.: 19 Cov.: 0 AF XY: 0.625 AC XY: 45 AN XY: 72

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.585 AC: 88774 AN: 151762 Hom.: 26463 Cov.: 30 AF XY: 0.582 AC XY: 43131 AN XY: 74168

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.532

Alfa AF: 0.593 Hom.: 40079

Bravo AF: 0.580

Asia WGS AF: 0.401 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.69
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2363561; hg19: chr1-215255307;