rs2294934

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB2	NM_001199862.2	c.425+99G>A		intron_variant		ENST00000378083.8	NP_001186791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB2	ENST00000378083.8	c.425+99G>A		intron_variant		2	NM_001199862.2	ENSP00000367323.3

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

Gnomad4 AFR exome AF: 0.0668

Gnomad4 AMR exome AF: 0.0766

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.101

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

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.0985

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0799 Hom.: 248

Bravo AF: 0.0954

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294934; hg19: chr1-6145407; COSMIC: COSV51235837; COSMIC: COSV51235837;