1-110601794-A-ATGTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004974.4(KCNA2):c.*1488_*1489insCACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (8 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (1 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335

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-A-ATGTG is Benign according to our data. Variant chr1-110601794-A-ATGTG is described in ClinVar as [Likely_benign]. Clinvar id is 1190501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0079 (1074/135946) while in subpopulation AFR AF= 0.0221 (758/34362). AF 95% confidence interval is 0.0208. There are 8 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 1070 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNA2	NM_004974.4	c.*1488_*1489insCACA		3_prime_UTR_variant	3/3	ENST00000316361.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1488_*1489insCACA		3_prime_UTR_variant	3/3	2	NM_004974.4	P1

Frequencies

GnomAD3 genomes AF: 0.00787 AC: 1070 AN: 135898 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00364

Gnomad ASJ AF: 0.00120

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.00711

Gnomad FIN AF: 0.000836

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.0107

GnomAD4 exome AF: 0.00290 AC: 2035 AN: 702496 Hom.: 1 Cov.: 6 AF XY: 0.00294 AC XY: 988 AN XY: 335700

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.00272

Gnomad4 SAS exome AF: 0.00697

Gnomad4 FIN exome AF: 0.00185

Gnomad4 NFE exome AF: 0.00253

Gnomad4 OTH exome AF: 0.00387

GnomAD4 genome AF: 0.00790 AC: 1074 AN: 135946 Hom.: 8 Cov.: 0 AF XY: 0.00804 AC XY: 526 AN XY: 65448

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00364

Gnomad4 ASJ AF: 0.00120

Gnomad4 EAS AF: 0.00403

Gnomad4 SAS AF: 0.00786

Gnomad4 FIN AF: 0.000836

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

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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: rs35728918; hg19: chr1-111144416;