rs1801471

Positions:

chr20-63407025-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_172107.4(KCNQ2):c.2238T>A(p.Pro746=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,522,048 control chromosomes in the GnomAD database, including 7,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 587 hom., cov: 33)

Exomes 𝑓: 0.096 ( 7189 hom. )

Consequence

KCNQ2
NM_172107.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.933

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 20-63407025-A-T is Benign according to our data. Variant chr20-63407025-A-T is described in ClinVar as [Benign]. Clinvar id is 129342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63407025-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.933 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ2	NM_172107.4 linkuse as main transcript	c.2238T>A	p.Pro746=	synonymous_variant	17/17	ENST00000359125.7	NP_742105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ2	ENST00000359125.7 linkuse as main transcript	c.2238T>A	p.Pro746=	synonymous_variant	17/17	1	NM_172107.4	ENSP00000352035	A1	O43526-1

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11555

AN:

152174

Hom.:

586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0699

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.0977

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0990

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.108

AC:

14010

AN:

130086

Hom.:

927

AF XY:

0.112

AC XY:

8046

AN XY:

71550

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0959

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.0965

AC:

132155

AN:

1369756

Hom.:

7189

Cov.:

AF XY:

0.0991

AC XY:

66784

AN XY:

673660

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.0948

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0932

Gnomad4 OTH exome

AF:

0.0900

GnomAD4 genome

AF:

0.0760

AC:

11567

AN:

152292

Hom.:

587

Cov.:

AF XY:

0.0780

AC XY:

5807

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.0696

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.0977

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0871

Hom.:

139

Bravo

AF:

0.0661

Asia WGS

AF:

0.176

AC:

610

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Eurofins Ntd Llc (ga)	May 17, 2016	- -
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 25% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 23. Only high quality variants are reported. -

Seizures, benign familial neonatal, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2016

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

- -

Developmental and epileptic encephalopathy, 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

DANN

Benign

0.73

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