rs11782118

Variant names:

• chr8-72937968-G-A
• rs11782118
• NM_004770.3:c.2613G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004770.3(KCNB2):​c.2613G>A​(p.Val871Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,696 control chromosomes in the GnomAD database, including 127,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9479 hom., cov: 32)
  • Exomes 𝑓: 0.39 (118294 hom.)
• Consequence: KCNB2 NM_004770.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.13
• Publications: 15 publications found

Genes affected

KCNB2 (HGNC:6232): (potassium voltage-gated channel subfamily B member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel. The gene is expressed in gastrointestinal smooth muscle cells. [provided by RefSeq, Jul 2008]

KCNB2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-72937968-G-A is Benign according to our data. Variant chr8-72937968-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	NM_004770.3	MANE Select	c.2613G>A	p.Val871Val	synonymous	Exon 3 of 3	NP_004761.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.2613G>A	p.Val871Val	synonymous	Exon 3 of 3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51334 AN: 151840 Hom.: 9480 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.334 AC: 83988 AN: 251170 AF XY: 0.338

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.361

Gnomad EAS exome AF: 0.0991

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.394 AC: 576587 AN: 1461736 Hom.: 118294 Cov.: 42 AF XY: 0.391 AC XY: 284449 AN XY: 727158

African (AFR) AF: 0.225 AC: 7525 AN: 33478

American (AMR) AF: 0.259 AC: 11600 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 9421 AN: 26128

East Asian (EAS) AF: 0.0932 AC: 3698 AN: 39694

South Asian (SAS) AF: 0.265 AC: 22887 AN: 86252

European-Finnish (FIN) AF: 0.406 AC: 21694 AN: 53414

Middle Eastern (MID) AF: 0.334 AC: 1927 AN: 5768

European-Non Finnish (NFE) AF: 0.428 AC: 475452 AN: 1111888

Other (OTH) AF: 0.371 AC: 22383 AN: 60394

GnomAD4 genome AF: 0.338 AC: 51350 AN: 151960 Hom.: 9479 Cov.: 32 AF XY: 0.335 AC XY: 24890 AN XY: 74250

African (AFR) AF: 0.226 AC: 9367 AN: 41442

American (AMR) AF: 0.309 AC: 4717 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.0967 AC: 500 AN: 5168

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4820

European-Finnish (FIN) AF: 0.421 AC: 4433 AN: 10540

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28578 AN: 67942

Other (OTH) AF: 0.345 AC: 728 AN: 2110

Alfa AF: 0.385 Hom.: 35389

Bravo AF: 0.325

Asia WGS AF: 0.229 AC: 795 AN: 3478

EpiCase AF: 0.416

EpiControl AF: 0.416

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	KCNB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11782118; hg19: chr8-73850203; COSMIC: COSV73053261;