chr1-6051648-C-G

Variant names:

• chr1-6051648-C-G
• NM_001199862.2:c.112C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001199862.2(KCNAB2):​c.112C>G​(p.Arg38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,381,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: KCNAB2 NM_001199862.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2577427).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNAB2	NM_001199862.2	c.112C>G	p.Arg38Gly	missense_variant	Exon 2 of 16	ENST00000378083.8	NP_001186791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNAB2	ENST00000378083.8	c.112C>G	p.Arg38Gly	missense_variant	Exon 2 of 16	2	NM_001199862.2	ENSP00000367323.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000130 AC: 18 AN: 1381836 Hom.: 0 Cov.: 31 AF XY: 0.0000132 AC XY: 9 AN XY: 681878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.072
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.086
Sift	Uncertain	0.010	D
Sift4G	Benign	0.25	T
Polyphen		0.14	B
Vest4		0.47
MutPred		0.40		Loss of MoRF binding (P = 0.0152);
MVP		0.13
MPC		1.3
ClinPred		0.98	D
GERP RS		4.3
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6111708;