rs2383869

Variant names:

• chr8-72654226-C-T
• rs2383869
• NM_004770.3:c.579+85913C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004770.3(KCNB2):​c.579+85913C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,076 control chromosomes in the GnomAD database, including 14,188 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 0.40 (14188 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 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.579+85913C>T		intron	N/A	NP_004761.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.579+85913C>T		intron	N/A	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61484 AN: 151958 Hom.: 14181 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.412

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 61519 AN: 152076 Hom.: 14188 Cov.: 32 AF XY: 0.401 AC XY: 29829 AN XY: 74318

African (AFR) AF: 0.194 AC: 8066 AN: 41530

American (AMR) AF: 0.517 AC: 7889 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3468

East Asian (EAS) AF: 0.191 AC: 985 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1424 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4761 AN: 10560

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35435 AN: 67960

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.472 Hom.: 17459

Bravo AF: 0.401

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		-0.43
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: rs2383869; hg19: chr8-73566461;