rs112410383

Variant names:

• chr1-110601794-A-G
• rs112410383
• NM_004974.4:c.*1489T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-110601794-A-G
• chr1-110601794-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004974.4(KCNA2):​c.*1489T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1567 hom., cov: 20)
  • Exomes 𝑓: 0.071 (2547 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNA2 NM_004974.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

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 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-110601794-A-G is Benign according to our data. Variant chr1-110601794-A-G is described in ClinVar as [Benign]. Clinvar id is 1241628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNA2	NM_004974.4	c.*1489T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000316361.10	NP_004965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNA2	ENST00000316361.10	c.*1489T>C		3_prime_UTR_variant	Exon 3 of 3	2	NM_004974.4	ENSP00000314520.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 17619 AN: 135424 Hom.: 1555 Cov.: 20

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0950

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.136

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0712 AC: 49753 AN: 699006 Hom.: 2547 Cov.: 11 AF XY: 0.0725 AC XY: 24199 AN XY: 333990

African (AFR) AF: 0.0694 AC: 1008 AN: 14530

American (AMR) AF: 0.282 AC: 1493 AN: 5296

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 754 AN: 9200

East Asian (EAS) AF: 0.385 AC: 5485 AN: 14258

South Asian (SAS) AF: 0.0855 AC: 1072 AN: 12538

European-Finnish (FIN) AF: 0.139 AC: 1414 AN: 10202

Middle Eastern (MID) AF: 0.0912 AC: 171 AN: 1876

European-Non Finnish (NFE) AF: 0.0597 AC: 36070 AN: 603834

Other (OTH) AF: 0.0838 AC: 2286 AN: 27272

GnomAD4 genome AF: 0.130 AC: 17648 AN: 135472 Hom.: 1567 Cov.: 20 AF XY: 0.137 AC XY: 8950 AN XY: 65214

African (AFR) AF: 0.111 AC: 3805 AN: 34218

American (AMR) AF: 0.282 AC: 3769 AN: 13386

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 312 AN: 3322

East Asian (EAS) AF: 0.367 AC: 1622 AN: 4422

South Asian (SAS) AF: 0.171 AC: 691 AN: 4046

European-Finnish (FIN) AF: 0.145 AC: 1211 AN: 8344

Middle Eastern (MID) AF: 0.109 AC: 30 AN: 274

European-Non Finnish (NFE) AF: 0.0908 AC: 5873 AN: 64706

Other (OTH) AF: 0.134 AC: 252 AN: 1880

Alfa AF: 0.139 Hom.: 53

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112410383; hg19: chr1-111144416;