20-63406349-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.*295C>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 0.0481 in 398,550 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (239 hom., cov: 33)
  • Exomes 𝑓: 0.050 (437 hom.)
• Consequence: KCNQ2 NM_172107.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.33

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=-0.98).
• BP6: Variant 20-63406349-G-A is Benign according to our data. Variant chr20-63406349-G-A is described in ClinVar as [Benign]. Clinvar id is 339325.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63406349-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ2	NM_172107.4	c.*295C>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.*295C>T		3_prime_UTR_variant	17/17	1	NM_172107.4	A1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6924 AN: 152074 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0510

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0498 AC: 12262 AN: 246358 Hom.: 437 Cov.: 2 AF XY: 0.0525 AC XY: 6640 AN XY: 126584

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0386

Gnomad4 EAS exome AF: 0.00195

Gnomad4 SAS exome AF: 0.0922

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0484

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.0455 AC: 6925 AN: 152192 Hom.: 239 Cov.: 33 AF XY: 0.0483 AC XY: 3594 AN XY: 74404

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0510

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0462 Hom.: 25

Bravo AF: 0.0474

Asia WGS AF: 0.0480 AC: 168 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 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.57
Dann	Benign	0.71

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: rs34690549; hg19: chr20-62037702;