Genetic Variant KCNAB2:c.425+99G>A (chr1-6085347-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

2 publications found

Variant links:

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]

KCNAB2 links:

LOC124903831 (HGNC:):

LOC124903831 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNAB2	NM_001199862.2 link	c.425+99G>A		intron_variant	Intron 6 of 15	ENST00000378083.8	NP_001186791.1	Q13303-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNAB2	ENST00000378083.8 link	c.425+99G>A		intron_variant	Intron 6 of 15	2	NM_001199862.2	ENSP00000367323.3		Q13303-3

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15315

AN:

152064

Hom.:

967

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3739

7478

11218

14957

18696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1346

2692

4038

5384

6730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15313

AN:

152182

Hom.:

964

Cov.:

AF XY:

0.102

AC XY:

7608

AN XY:

74392

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0988

AC:

6720

AN:

68014

Other (OTH)

AF:

0.0881

AC:

186

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

687

1374

2061

2748

3435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.8

(source)

DANN

Benign

0.69

PhyloP100

0.042

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over