rs3800779

Variant names:

• chr7-150974126-C-A
• rs3800779
• NM_000238.4:c.307+585G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-150974126-C-A
• chr7-150974126-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000238.4(KCNH2):​c.307+585G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,012 control chromosomes in the GnomAD database, including 5,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5883 hom., cov: 33)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 13 publications found

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), G2P, Ambry Genetics
• short QT syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000238.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH2	NM_000238.4	MANE Select	c.307+585G>T		intron	N/A	NP_000229.1	A0A090N8Q0
	KCNH2	NM_172056.3		c.307+585G>T		intron	N/A	NP_742053.1	Q12809-5
	KCNH2	NM_001406755.1		c.130+585G>T		intron	N/A	NP_001393684.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH2	ENST00000262186.10	TSL:1 MANE Select	c.307+585G>T		intron	N/A	ENSP00000262186.5	Q12809-1
	KCNH2	ENST00000713710.1		c.307+585G>T		intron	N/A	ENSP00000519013.1	A0AAQ5BGR0
	KCNH2	ENST00000713701.1		c.7+244G>T		intron	N/A	ENSP00000519004.1	A0AAQ5BGQ9

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39925 AN: 151894 Hom.: 5888 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 39923 AN: 152012 Hom.: 5883 Cov.: 33 AF XY: 0.259 AC XY: 19264 AN XY: 74294

African (AFR) AF: 0.135 AC: 5612 AN: 41482

American (AMR) AF: 0.284 AC: 4344 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1132 AN: 3470

East Asian (EAS) AF: 0.106 AC: 544 AN: 5156

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2938 AN: 10568

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22786 AN: 67932

Other (OTH) AF: 0.265 AC: 558 AN: 2104

Alfa AF: 0.273 Hom.: 2048

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3800779; hg19: chr7-150671214; COSMIC: COSV51131278;