1-110601828-G-GTGTGTGTA

Position:

• chr1-110601828-G-GTGTGTGTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004974.4(KCNA2):​c.*1454_*1455insTACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 142,244 control chromosomes in the GnomAD database, including 221 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (221 hom., cov: 28)
  • Exomes 𝑓: 0.0051 (12 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600

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]

KCNA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110601828-G-GTGTGTGTA is Benign according to our data. Variant chr1-110601828-G-GTGTGTGTA is described in ClinVar as [Benign]. Clinvar id is 1247502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1454_*1455insTACACACA		3_prime_UTR_variant	3/3	ENST00000316361.10	NP_004965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000316361	c.*1454_*1455insTACACACA		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 5866 AN: 142166 Hom.: 218 Cov.: 28

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0296

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0467

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00506 AC: 5505 AN: 1087838 Hom.: 12 Cov.: 27 AF XY: 0.00539 AC XY: 2814 AN XY: 521930

Gnomad4 AFR exome AF: 0.00654

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.0577

Gnomad4 SAS exome AF: 0.00465

Gnomad4 FIN exome AF: 0.0219

Gnomad4 NFE exome AF: 0.00249

Gnomad4 OTH exome AF: 0.00810

GnomAD4 genome AF: 0.0413 AC: 5874 AN: 142244 Hom.: 221 Cov.: 28 AF XY: 0.0445 AC XY: 3062 AN XY: 68786

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0834

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0480

Gnomad4 NFE AF: 0.0262

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0178 Hom.: 10

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs763912060; hg19: chr1-111144450;