1-110601828-G-A

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.*1455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,235,860 control chromosomes in the GnomAD database, including 1,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (1072 hom., cov: 27)
  • Exomes 𝑓: 0.0097 (587 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.312

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=-0.97).
• BP6: Variant 1-110601828-G-A is Benign according to our data. Variant chr1-110601828-G-A is described in ClinVar as [Benign]. Clinvar id is 1246346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1455C>T		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1455C>T		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9329 AN: 143378 Hom.: 1066 Cov.: 27

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00409

Gnomad EAS AF: 0.00244

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.000422

Gnomad MID AF: 0.0390

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0501

GnomAD4 exome AF: 0.00965 AC: 10545 AN: 1092408 Hom.: 587 Cov.: 25 AF XY: 0.00887 AC XY: 4648 AN XY: 524112

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.00463

Gnomad4 EAS exome AF: 0.00991

Gnomad4 SAS exome AF: 0.00828

Gnomad4 FIN exome AF: 0.00271

Gnomad4 NFE exome AF: 0.00427

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0652 AC: 9358 AN: 143452 Hom.: 1072 Cov.: 27 AF XY: 0.0633 AC XY: 4396 AN XY: 69460

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.00409

Gnomad4 EAS AF: 0.00245

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000422

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.00125 Hom.: 0

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

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.33
Dann	Benign	0.16

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: rs6675561; hg19: chr1-111144450;