NM_000238.4:c.76+8G>A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000238.4(KCNH2):c.76+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_000238.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- long QT syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- long QT syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- short QT syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- short QT syndrome type 1Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- Brugada syndromeInheritance: AD Classification: MODERATE, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.76+8G>A | splice_region_variant, intron_variant | Intron 1 of 14 | ENST00000262186.10 | NP_000229.1 | ||
KCNH2 | NM_172056.3 | c.76+8G>A | splice_region_variant, intron_variant | Intron 1 of 8 | NP_742053.1 | |||
KCNH2 | NR_176254.1 | n.484+8G>A | splice_region_variant, intron_variant | Intron 1 of 14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.76+8G>A | splice_region_variant, intron_variant | Intron 1 of 14 | 1 | NM_000238.4 | ENSP00000262186.5 | |||
KCNH2 | ENST00000713710.1 | c.76+8G>A | splice_region_variant, intron_variant | Intron 1 of 14 | ENSP00000519013.1 | |||||
KCNH2 | ENST00000532957.5 | n.299+8G>A | splice_region_variant, intron_variant | Intron 1 of 8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 27
GnomAD2 exomes AF: 0.00 AC: 0AN: 224218 AF XY: 0.00
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1437362Hom.: 0 Cov.: 26 AF XY: 0.00000140 AC XY: 1AN XY: 714486 show subpopulations
GnomAD4 genome Cov.: 27
ClinVar
Submissions by phenotype
Long QT syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at