rs3778872

Variant names:

• chr7-150972888-C-G
• rs3778872
• NM_000238.4:c.307+1823G>C

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+1823G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,152 control chromosomes in the GnomAD database, including 4,022 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 0.22 (4022 hom., cov: 33)
• Consequence: KCNH2 NM_000238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 19 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), 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNH2	NM_000238.4	c.307+1823G>C		intron_variant	Intron 2 of 14	ENST00000262186.10	NP_000229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNH2	ENST00000262186.10	c.307+1823G>C		intron_variant	Intron 2 of 14	1	NM_000238.4	ENSP00000262186.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32869 AN: 152034 Hom.: 4019 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.216 AC: 32884 AN: 152152 Hom.: 4022 Cov.: 33 AF XY: 0.217 AC XY: 16169 AN XY: 74390

African (AFR) AF: 0.313 AC: 12981 AN: 41482

American (AMR) AF: 0.121 AC: 1848 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1638 AN: 5164

South Asian (SAS) AF: 0.199 AC: 962 AN: 4824

European-Finnish (FIN) AF: 0.250 AC: 2645 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11447 AN: 68010

Other (OTH) AF: 0.195 AC: 413 AN: 2114

Alfa AF: 0.199 Hom.: 432

Bravo AF: 0.213

Asia WGS AF: 0.237 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.72
PhyloP100		-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: rs3778872; hg19: chr7-150669976;