rs2294934

Variant names:

• chr1-6085347-G-A
• rs2294934
• NM_001199862.2:c.425+99G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-6085347-G-A
• chr1-6085347-G-C
• chr1-6085347-G-T

Variant summary

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

The NM_001199862.2(KCNAB2):​c.425+99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 987,398 control chromosomes in the GnomAD database, including 7,377 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 0.10 (964 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6413 hom.)
• Consequence: KCNAB2 NM_001199862.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 2 publications found

Genes affected

KCNAB2 (HGNC:6229): (potassium voltage-gated channel subfamily A regulatory beta subunit 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, shaker-related subfamily. This member is one of the beta subunits, which are auxiliary proteins associating with functional Kv-alpha subunits. This member alters functional properties of the KCNA4 gene product. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2010]

LOC124903831 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199862.2. 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
	KCNAB2	NM_001199862.2	MANE Select	c.425+99G>A		intron	N/A	NP_001186791.1	Q13303-3
	KCNAB2	NM_001199860.2		c.326+99G>A		intron	N/A	NP_001186789.1	Q13303-1
	KCNAB2	NM_001199861.2		c.326+99G>A		intron	N/A	NP_001186790.1	Q13303-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB2	ENST00000378083.8	TSL:2 MANE Select	c.425+99G>A		intron	N/A	ENSP00000367323.3	Q13303-3
	KCNAB2	ENST00000341524.6	TSL:1	c.326+99G>A		intron	N/A	ENSP00000340824.2	A0A5F9UN28
	KCNAB2	ENST00000378097.6	TSL:1	c.326+99G>A		intron	N/A	ENSP00000367337.1	Q13303-1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15315 AN: 152064 Hom.: 967 Cov.: 33

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0835

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.108 AC: 90405 AN: 835216 Hom.: 6413 AF XY: 0.109 AC XY: 47562 AN XY: 435122

African (AFR) AF: 0.0668 AC: 1400 AN: 20968

American (AMR) AF: 0.0766 AC: 2939 AN: 38382

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2053 AN: 20492

East Asian (EAS) AF: 0.370 AC: 13366 AN: 36076

South Asian (SAS) AF: 0.133 AC: 9247 AN: 69616

European-Finnish (FIN) AF: 0.113 AC: 5836 AN: 51586

Middle Eastern (MID) AF: 0.100 AC: 299 AN: 2988

European-Non Finnish (NFE) AF: 0.0923 AC: 51344 AN: 556188

Other (OTH) AF: 0.101 AC: 3921 AN: 38920

GnomAD4 genome AF: 0.101 AC: 15313 AN: 152182 Hom.: 964 Cov.: 33 AF XY: 0.102 AC XY: 7608 AN XY: 74392

African (AFR) AF: 0.0716 AC: 2972 AN: 41528

American (AMR) AF: 0.0833 AC: 1274 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 342 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1759 AN: 5150

South Asian (SAS) AF: 0.146 AC: 704 AN: 4830

European-Finnish (FIN) AF: 0.114 AC: 1202 AN: 10584

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6720 AN: 68014

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.0815 Hom.: 293

Bravo AF: 0.0954

Asia WGS AF: 0.206 AC: 715 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	4.8
DANN	Benign	0.69
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2294934;

hg19: chr1-6145407;

COSMIC: COSV51235837;

COSMIC: COSV51235837;