1-110601790-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004974.4(KCNA2):c.*1493T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 1,139,810 control chromosomes in the GnomAD database, including 2,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (1082 hom., cov: 28)
  • Exomes 𝑓: 0.024 (1509 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.146

Genes affected

KCNA2 (HGNC:6220): (potassium voltage-gated channel subfamily A member 2) Potassium 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 contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-110601790-A-G is Benign according to our data. Variant chr1-110601790-A-G is described in ClinVar as [Benign]. Clinvar id is 1269688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1493T>C		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1493T>C		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 13489 AN: 136590 Hom.: 1070 Cov.: 28

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.0566

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0636

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0500

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0236 AC: 23650 AN: 1003134 Hom.: 1509 Cov.: 23 AF XY: 0.0242 AC XY: 11489 AN XY: 475262

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0342

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.0744

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0354

GnomAD4 genome AF: 0.0988 AC: 13508 AN: 136676 Hom.: 1082 Cov.: 28 AF XY: 0.106 AC XY: 7025 AN XY: 66112

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.0636

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0820 Hom.: 24

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs201924903; hg19: chr1-111144412;