1-110601777-A-AAT

Position:

• chr1-110601777-A-AAT

Variant summary

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

The NM_004974.4(KCNA2):​c.*1504_*1505dupAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 139,726 control chromosomes in the GnomAD database, including 2,479 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2479 hom., cov: 22)
  • Exomes 𝑓: 0.13 (632 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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 1-110601777-A-AAT is Benign according to our data. Variant chr1-110601777-A-AAT is described in ClinVar as [Benign]. Clinvar id is 1270237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1504_*1505dupAT		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.*1504_*1505dupAT		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.188 AC: 26243 AN: 139644 Hom.: 2479 Cov.: 22

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.215

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.132 AC: 103734 AN: 782948 Hom.: 632 Cov.: 15 AF XY: 0.134 AC XY: 49393 AN XY: 369264

Gnomad4 AFR exome AF: 0.0941

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0753

Gnomad4 SAS exome AF: 0.0977

Gnomad4 FIN exome AF: 0.0965

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.188 AC: 26241 AN: 139726 Hom.: 2479 Cov.: 22 AF XY: 0.183 AC XY: 12332 AN XY: 67466

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.215

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: rs149560146; hg19: chr1-111144399;