rs6700661

Variant names:

• chr1-110526711-T-G
• rs6700661
• ENST00000779684.1:n.331T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000779684.1(ENSG00000301555):​n.331T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,152 control chromosomes in the GnomAD database, including 2,254 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2254 hom., cov: 32)
• Consequence: ENSG00000301555 ENST00000779684.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.38
• Publications: 2 publications found

Genes affected

ENSG00000301555 (HGNC:):

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 32

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904292	XR_007066353.1	n.312T>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301555	ENST00000779684.1	n.331T>G		non_coding_transcript_exon_variant	Exon 2 of 2
KCNA2	ENST00000640680.1	n.2732-4413A>C		intron_variant	Intron 6 of 8	5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25183 AN: 152034 Hom.: 2251 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25218 AN: 152152 Hom.: 2254 Cov.: 32 AF XY: 0.164 AC XY: 12164 AN XY: 74394

African (AFR) AF: 0.222 AC: 9211 AN: 41484

American (AMR) AF: 0.157 AC: 2399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.0461 AC: 239 AN: 5180

South Asian (SAS) AF: 0.211 AC: 1013 AN: 4812

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9900 AN: 67994

Other (OTH) AF: 0.166 AC: 351 AN: 2110

Alfa AF: 0.155 Hom.: 1289

Bravo AF: 0.169

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.045
DANN	Benign	0.49
PhyloP100		-4.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6700661; hg19: chr1-111069333;