1-110601794-A-ATG

Position:

• chr1-110601794-A-ATG

Variant summary

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

The NM_004974.4(KCNA2):​c.*1487_*1488dupCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1419 hom., cov: 0)
  • Exomes 𝑓: 0.14 (222 hom.)
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: 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]

KCNA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-110601794-A-ATG is Benign according to our data. Variant chr1-110601794-A-ATG is described in ClinVar as [Benign]. Clinvar id is 1251062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1487_*1488dupCA		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.*1487_*1488dupCA		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.133 AC: 17989 AN: 135618 Hom.: 1417 Cov.: 0

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0544

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.135 AC: 91742 AN: 677428 Hom.: 222 Cov.: 6 AF XY: 0.136 AC XY: 43917 AN XY: 323568

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.0848

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.133 AC: 17986 AN: 135670 Hom.: 1419 Cov.: 0 AF XY: 0.128 AC XY: 8363 AN XY: 65298

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.113

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: rs35728918; hg19: chr1-111144416;