1-215195099-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001017425.3(KCNK2):c.963+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,586,958 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (12 hom.)
• Consequence: KCNK2 NM_001017425.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002276
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.445

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-215195099-A-C is Benign according to our data. Variant chr1-215195099-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 785792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 206 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.963+7A>C		splice_region_variant, intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.963+7A>C		splice_region_variant, intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152210 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00129 AC: 305 AN: 235992 Hom.: 2 AF XY: 0.00146 AC XY: 186 AN XY: 127596

Gnomad AFR exome AF: 0.000254

Gnomad AMR exome AF: 0.000327

Gnomad ASJ exome AF: 0.000542

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000439

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.00246

Gnomad OTH exome AF: 0.000885

GnomAD4 exome AF: 0.00192 AC: 2758 AN: 1434630 Hom.: 12 Cov.: 29 AF XY: 0.00188 AC XY: 1340 AN XY: 712912

Gnomad4 AFR exome AF: 0.000338

Gnomad4 AMR exome AF: 0.000294

Gnomad4 ASJ exome AF: 0.000318

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000483

Gnomad4 FIN exome AF: 0.0000573

Gnomad4 NFE exome AF: 0.00237

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152328 Hom.: 1 Cov.: 33 AF XY: 0.00123 AC XY: 92 AN XY: 74504

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00146

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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: rs80246222; hg19: chr1-215368442;