20-63406396-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172107.4(KCNQ2):c.*248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 548,550 control chromosomes in the GnomAD database, including 3,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (539 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2627 hom.)
• Consequence: KCNQ2 NM_172107.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

Genes affected

KCNQ2 (HGNC:6296): (potassium voltage-gated channel subfamily Q member 2) The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-63406396-G-A is Benign according to our data. Variant chr20-63406396-G-A is described in ClinVar as [Benign]. Clinvar id is 1259970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ2	NM_172107.4	c.*248C>T		3_prime_UTR_variant	17/17	ENST00000359125.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ2	ENST00000359125.7	c.*248C>T		3_prime_UTR_variant	17/17	1	NM_172107.4	A1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5139 AN: 152160 Hom.: 539 Cov.: 33

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0496 AC: 19643 AN: 396272 Hom.: 2627 Cov.: 4 AF XY: 0.0477 AC XY: 9849 AN XY: 206348

Gnomad4 AFR exome AF: 0.00486

Gnomad4 AMR exome AF: 0.0353

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.0670

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0337 AC: 5135 AN: 152278 Hom.: 539 Cov.: 33 AF XY: 0.0389 AC XY: 2899 AN XY: 74452

Gnomad4 AFR AF: 0.00452

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.0267

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0104 Hom.: 2

Bravo AF: 0.0309

Asia WGS AF: 0.182 AC: 632 AN: 3478

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

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.8
Dann	Benign	0.83

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: rs6122440; hg19: chr20-62037749;