1-110601788-A-G

Position:

• chr1-110601788-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004974.4(KCNA2):​c.*1495T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 138,228 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 30)
  • Exomes 𝑓: 0.00059 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.523

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-110601788-A-G is Benign according to our data. Variant chr1-110601788-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1192746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00551 (762/138228) while in subpopulation EAS AF= 0.017 (82/4822). AF 95% confidence interval is 0.014. There are 5 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 762 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1495T>C		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.*1495T>C		3_prime_UTR_variant	3/3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.00547 AC: 755 AN: 138142 Hom.: 5 Cov.: 30

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00960

Gnomad ASJ AF: 0.00557

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.00697

Gnomad FIN AF: 0.000620

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000762

Gnomad OTH AF: 0.00780

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000586 AC: 611 AN: 1041860 Hom.: 1 Cov.: 24 AF XY: 0.000584 AC XY: 288 AN XY: 493198

Gnomad4 AFR exome AF: 0.00322

Gnomad4 AMR exome AF: 0.00901

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.00879

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.000686

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00551 AC: 762 AN: 138228 Hom.: 5 Cov.: 30 AF XY: 0.00535 AC XY: 359 AN XY: 67110

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00959

Gnomad4 ASJ AF: 0.00557

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.00697

Gnomad4 FIN AF: 0.000620

Gnomad4 NFE AF: 0.000762

Gnomad4 OTH AF: 0.00772

Alfa AF: 0.00331 Hom.: 0

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

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.74

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: rs1403613919; hg19: chr1-111144410;