rs863224336

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_000238.4(KCNH2):c.27G>T(p.Ala9Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,574,688 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. A9A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNH2
NM_000238.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.930

Publications

3 publications found

Variant links:

Genes affected

KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]

KCNH2 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
short QT syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
short QT syndrome type 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp

KCNH2 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=-0.36).

BP6

Variant 7-150977887-C-A is Benign according to our data. Variant chr7-150977887-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 215663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
KCNH2	NM_000238.4 link	c.27G>T	p.Ala9Ala	synonymous_variant	Exon 1 of 15	ENST00000262186.10	NP_000229.1
KCNH2	NM_172056.3 link	c.27G>T	p.Ala9Ala	synonymous_variant	Exon 1 of 9		NP_742053.1
KCNH2	NR_176254.1 link	n.435G>T		non_coding_transcript_exon_variant	Exon 1 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KCNH2	ENST00000262186.10 link	c.27G>T	p.Ala9Ala	synonymous_variant	Exon 1 of 15	1	NM_000238.4	ENSP00000262186.5
KCNH2	ENST00000713710.1 link	c.27G>T	p.Ala9Ala	synonymous_variant	Exon 1 of 15			ENSP00000519013.1
KCNH2	ENST00000532957.5 link	n.250G>T		non_coding_transcript_exon_variant	Exon 1 of 9	2

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

146784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1427904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32496

American (AMR)

AF:

0.00

AC:

AN:

43772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

37306

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4886

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092522

Other (OTH)

AF:

0.0000171

AC:

AN:

58350

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

AF:

0.0000136

AC:

AN:

146784

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40102

American (AMR)

AF:

0.000135

AC:

AN:

14818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4618

South Asian (SAS)

AF:

0.00

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66522

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:2

Apr 29, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 17, 2023

All of Us Research Program, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cardiac arrhythmia

Benign:1

Oct 09, 2019

Color Diagnostics, LLC DBA Color Health

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

-0.36

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.93

PromoterAI

-0.011

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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