1-110593989-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.*9294C>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 0.0876 in 1,545,932 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (1333 hom., cov: 30)
  • Exomes 𝑓: 0.087 (10116 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.795

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=-0.67).
• BP6: Variant 1-110593989-G-A is Benign according to our data. Variant chr1-110593989-G-A is described in ClinVar as [Benign]. Clinvar id is 1257086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*9294C>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.*9294C>T		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14474 AN: 151948 Hom.: 1333 Cov.: 30

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0573

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0868 AC: 120964 AN: 1393866 Hom.: 10116 Cov.: 31 AF XY: 0.0887 AC XY: 60978 AN XY: 687442

Gnomad4 AFR exome AF: 0.0524

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.0709

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0607

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0952 AC: 14477 AN: 152066 Hom.: 1333 Cov.: 30 AF XY: 0.105 AC XY: 7779 AN XY: 74332

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.0776

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0718 Hom.: 116

Bravo AF: 0.0994

Asia WGS AF: 0.301 AC: 1043 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
Dann	Benign	0.73

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: rs17026168; hg19: chr1-111136611; COSMIC: COSV104424803; COSMIC: COSV104424803;