rs41311012

Variant names:

• chr7-150955600-C-G
• rs41311012
• ENST00000330883.9:c.-97G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-150955600-C-G
• chr7-150955600-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172057.3(KCNH2):​c.-97G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNH2 NM_172057.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172057.3. 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.1128+1691G>C		intron	N/A	NP_000229.1
	KCNH2	NM_172057.3		c.-97G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_742054.1
	KCNH2	NM_001204798.2		c.-97G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001191727.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNH2	ENST00000330883.9	TSL:1	c.-97G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000328531.4
	KCNH2	ENST00000330883.9	TSL:1	c.-97G>C		5_prime_UTR	Exon 1 of 11	ENSP00000328531.4
	KCNH2	ENST00000262186.10	TSL:1 MANE Select	c.1128+1691G>C		intron	N/A	ENSP00000262186.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1288502 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 624596

African (AFR) AF: 0.00 AC: 0 AN: 27996

American (AMR) AF: 0.00 AC: 0 AN: 20964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18944

East Asian (EAS) AF: 0.00 AC: 0 AN: 34370

South Asian (SAS) AF: 0.00 AC: 0 AN: 62814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029844

Other (OTH) AF: 0.00 AC: 0 AN: 53284

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.35
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41311012; hg19: chr7-150652688;