chr1-215194960-C-T

Variant names:

• chr1-215194960-C-T
• rs149941939
• NM_001017425.3:c.831C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001017425.3(KCNK2):​c.831C>T​(p.Ser277Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,612,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: KCNK2 NM_001017425.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-215194960-C-T is Benign according to our data. Variant chr1-215194960-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 772824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.
• BS2: High AC in GnomAd4 at 65 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017425.3. 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_001017425.3	MANE Select	c.831C>T	p.Ser277Ser	synonymous	Exon 6 of 7	NP_001017425.2	O95069-1
	KCNK2	NM_001017424.3		c.819C>T	p.Ser273Ser	synonymous	Exon 6 of 7	NP_001017424.1	U3N834
	KCNK2	NM_014217.4		c.786C>T	p.Ser262Ser	synonymous	Exon 6 of 7	NP_055032.1	O95069-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.831C>T	p.Ser277Ser	synonymous	Exon 6 of 7	ENSP00000394033.2	O95069-1
	KCNK2	ENST00000391895.6	TSL:1	c.819C>T	p.Ser273Ser	synonymous	Exon 6 of 7	ENSP00000375765.2	O95069-3
	KCNK2	ENST00000391894.6	TSL:1	c.786C>T	p.Ser262Ser	synonymous	Exon 6 of 7	ENSP00000375764.2	O95069-2

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 151968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 250972 AF XY: 0.000103

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 109 AN: 1460762 Hom.: 0 Cov.: 30 AF XY: 0.0000715 AC XY: 52 AN XY: 726768

African (AFR) AF: 0.00207 AC: 69 AN: 33408

American (AMR) AF: 0.000134 AC: 6 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111326

Other (OTH) AF: 0.000232 AC: 14 AN: 60336

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28 AN XY: 74314

African (AFR) AF: 0.00142 AC: 59 AN: 41496

American (AMR) AF: 0.000327 AC: 5 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.000499

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.27
DANN	Benign	0.44
PhyloP100		-2.1
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs149941939; hg19: chr1-215368303; COSMIC: COSV67203046;