rs2297385

Positions:

chr20-63439613-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172107.4(KCNQ2):c.912C>T(p.Phe304=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0843 in 1,612,774 control chromosomes in the GnomAD database, including 9,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 1029 hom., cov: 33)

Exomes 𝑓: 0.085 ( 8770 hom. )

Consequence

KCNQ2
NM_172107.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.80

Variant links:

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]

KCNQ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008976191).

BP6

Variant 20-63439613-G-A is Benign according to our data. Variant chr20-63439613-G-A is described in ClinVar as [Benign]. Clinvar id is 129345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63439613-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ2	NM_172107.4 linkuse as main transcript	c.912C>T	p.Phe304=	synonymous_variant	6/17	ENST00000359125.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ2	ENST00000359125.7 linkuse as main transcript	c.912C>T	p.Phe304=	synonymous_variant	6/17	1	NM_172107.4	A1	O43526-1

Frequencies

GnomAD3 genomes

AF:

0.0816

AC:

12427

AN:

152210

Hom.:

1030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0888

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0937

GnomAD3 exomes

AF:

0.120

AC:

30118

AN:

250874

Hom.:

3072

AF XY:

0.119

AC XY:

16164

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0957

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.0840

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0845

AC:

123473

AN:

1460446

Hom.:

8770

Cov.:

AF XY:

0.0864

AC XY:

62811

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.0903

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0834

Gnomad4 NFE exome

AF:

0.0655

Gnomad4 OTH exome

AF:

0.0973

GnomAD4 genome

AF:

0.0815

AC:

12420

AN:

152328

Hom.:

1029

Cov.:

AF XY:

0.0881

AC XY:

6561

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.0922

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0888

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.0927

Alfa

AF:

0.0770

Hom.:

799

Bravo

AF:

0.0829

TwinsUK

AF:

0.0636

AC:

236

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.0673

AC:

579

ExAC

AF:

0.114

AC:

13856

Asia WGS

AF:

0.256

AC:

887

AN:

3478

EpiCase

AF:

0.0782

EpiControl

AF:

0.0809

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 19. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.2

DANN

Benign

0.66

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0090

MutationTaster

Benign

3.8e-22

P;P;P;P;P;P;P;P;P;P;P;P

Sift4G

Pathogenic

0.0

GERP RS

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over