20-63408500-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS2

The NM_172107.4(KCNQ2):c.1800G>C(p.Thr600Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T600T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KCNQ2
NM_172107.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.49

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 7
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
neonatal encephalopathy with non-epileptic myoclonus
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neonatal-onset developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
seizures, benign familial neonatal, 1
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
seizures, benign familial neonatal, 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
benign familial infantile epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
benign familial neonatal-infantile seizures
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
benign neonatal seizures
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KCNQ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 20-63408500-C-G is Benign according to our data. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63408500-C-G is described in CliVar as Likely_benign. Clinvar id is 1581467.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.49 with no splicing effect.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ2	NM_172107.4 link	c.1800G>C	p.Thr600Thr	synonymous_variant	Exon 16 of 17	ENST00000359125.7	NP_742105.1	O43526-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ2	ENST00000359125.7 link	c.1800G>C	p.Thr600Thr	synonymous_variant	Exon 16 of 17	1	NM_172107.4	ENSP00000352035.2		O43526-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000415

AC:

AN:

240752

AF XY:

0.00000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000924

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457138

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26022

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110694

Other (OTH)

AF:

0.00

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy

Benign:1

Nov 27, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.77

CADD

Benign

0.0070

(source)

DANN

Benign

0.78

PhyloP100

-6.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over