rs772037564
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000238.4(KCNH2):c.697G>T(p.Ala233Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 1,457,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A233T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000238.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.697G>T | p.Ala233Ser | missense_variant | 4/15 | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.697G>T | p.Ala233Ser | missense_variant | 4/15 | 1 | NM_000238.4 | P1 | |
KCNH2 | ENST00000532957.5 | n.920G>T | non_coding_transcript_exon_variant | 4/9 | 2 | ||||
KCNH2 | ENST00000684241.1 | n.1530G>T | non_coding_transcript_exon_variant | 2/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000593 AC: 9AN: 151862Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000228 AC: 18AN: 78984Hom.: 0 AF XY: 0.000285 AC XY: 13AN XY: 45542
GnomAD4 exome AF: 0.0000613 AC: 80AN: 1305430Hom.: 2 Cov.: 32 AF XY: 0.0000885 AC XY: 57AN XY: 643832
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 151970Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 22, 2017 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at