rs1555518481
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_000196.4(HSD11B2):c.266G>A(p.Gly89Asp) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/25 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000196.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD11B2 | NM_000196.4 | c.266G>A | p.Gly89Asp | missense_variant, splice_region_variant | 2/5 | ENST00000326152.6 | |
HSD11B2 | XM_047434048.1 | c.-47G>A | splice_region_variant, 5_prime_UTR_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD11B2 | ENST00000326152.6 | c.266G>A | p.Gly89Asp | missense_variant, splice_region_variant | 2/5 | 1 | NM_000196.4 | P1 | |
HSD11B2 | ENST00000567684.2 | n.129G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/4 | 3 | ||||
HSD11B2 | ENST00000566606.1 | c.*67G>A | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460588Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726626
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Apparent mineralocorticoid excess Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Jan 25, 2018 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29229831, 25593612, 24123366) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 16, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at