1-110601794-ATGTG-A

Position:

• chr1-110601794-ATGTG-A

Variant summary

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

The NM_004974.4(KCNA2):​c.*1485_*1488del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 830,402 control chromosomes in the GnomAD database, including 391 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (194 hom., cov: 0)
  • Exomes 𝑓: 0.060 (197 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.391

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 -10 ACMG points.

• BP6: Variant 1-110601794-ATGTG-A is Benign according to our data. Variant chr1-110601794-ATGTG-A is described in ClinVar as [Benign]. Clinvar id is 1274548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1485_*1488del		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1485_*1488del		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7060 AN: 135822 Hom.: 195 Cov.: 0

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.0651

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00916

Gnomad SAS AF: 0.0444

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0238

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0602 AC: 41819 AN: 694534 Hom.: 197 AF XY: 0.0602 AC XY: 19989 AN XY: 331932

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0558

Gnomad4 ASJ exome AF: 0.0322

Gnomad4 EAS exome AF: 0.00845

Gnomad4 SAS exome AF: 0.0615

Gnomad4 FIN exome AF: 0.0666

Gnomad4 NFE exome AF: 0.0618

Gnomad4 OTH exome AF: 0.0551

GnomAD4 genome AF: 0.0519 AC: 7056 AN: 135868 Hom.: 194 Cov.: 0 AF XY: 0.0503 AC XY: 3292 AN XY: 65406

Gnomad4 AFR AF: 0.0599

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00918

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.0413

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

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: rs35728918; hg19: chr1-111144416;