Genetic Variant KCNK2:c.35-4404T>C (chr1-215081964-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.416

Publications

7 publications found

Variant links:

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]

KCNK2 links:

LOC124904511 (HGNC:):

LOC124904511 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017424.3. 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
	KCNK2	NM_001017424.3		c.35-4404T>C		intron	N/A	NP_001017424.1	U3N834

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNK2	ENST00000391895.6	TSL:1	c.35-4404T>C	intron	N/A	ENSP00000375765.2	O95069-3
KCNK2	ENST00000467031.5	TSL:1	n.35-4404T>C	intron	N/A	ENSP00000420203.1	O95069-4
KCNK2	ENST00000478774.5	TSL:4	c.-144+103T>C	intron	N/A	ENSP00000420569.1	C9JDK1

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88719

AN:

151644

Hom.:

26441

Cov.:

show subpopulations

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:

AN:

102

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.603

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.585

AC:

88774

AN:

151762

Hom.:

26463

Cov.:

AF XY:

0.582

AC XY:

43131

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.536

AC:

22150

AN:

41362

American (AMR)

AF:

0.564

AC:

8604

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1645

AN:

3466

East Asian (EAS)

AF:

0.556

AC:

2848

AN:

5124

South Asian (SAS)

AF:

0.298

AC:

1435

AN:

4808

European-Finnish (FIN)

AF:

0.725

AC:

7644

AN:

10544

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42518

AN:

67898

Other (OTH)

AF:

0.532

AC:

1118

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1849

3698

5546

7395

9244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.599

Hom.:

93536

Bravo

AF:

0.580

Asia WGS

AF:

0.401

AC:

1395

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.69

(source)

DANN

Benign

0.41

PhyloP100

-0.42

PromoterAI

0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over