rs2269001

Variant names:

• chr7-150954728-G-A
• rs2269001
• NM_000238.4:c.1129-1875C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-150954728-G-A
• chr7-150954728-G-C
• chr7-150954728-G-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.1129-1875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,074 control chromosomes in the GnomAD database, including 6,218 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 0.27 (6218 hom., cov: 33)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 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.1129-1875C>T		intron	N/A	NP_000229.1	A0A090N8Q0
	KCNH2	NM_001406753.1		c.841-1875C>T		intron	N/A	NP_001393682.1	Q12809-7
	KCNH2	NM_172056.3		c.1129-1875C>T		intron	N/A	NP_742053.1	Q12809-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH2	ENST00000262186.10	TSL:1 MANE Select	c.1129-1875C>T		intron	N/A	ENSP00000262186.5	Q12809-1
	KCNH2	ENST00000330883.9	TSL:1	c.108+668C>T		intron	N/A	ENSP00000328531.4	Q12809-2
	KCNH2	ENST00000461280.2	TSL:1	n.426+668C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41135 AN: 151956 Hom.: 6200 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.271 AC: 41187 AN: 152074 Hom.: 6218 Cov.: 33 AF XY: 0.279 AC XY: 20725 AN XY: 74318

African (AFR) AF: 0.281 AC: 11669 AN: 41482

American (AMR) AF: 0.333 AC: 5090 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3466

East Asian (EAS) AF: 0.647 AC: 3341 AN: 5164

South Asian (SAS) AF: 0.312 AC: 1507 AN: 4824

European-Finnish (FIN) AF: 0.315 AC: 3332 AN: 10580

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14310 AN: 67956

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.239 Hom.: 650

Bravo AF: 0.278

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2269001; hg19: chr7-150651816;