rs121917833
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000196.4(HSD11B2):c.667G>A(p.Asp223Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000991 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000196.4 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD11B2 | NM_000196.4 | c.667G>A | p.Asp223Asn | missense_variant, splice_region_variant | 4/5 | ENST00000326152.6 | |
HSD11B2 | XM_047434048.1 | c.355G>A | p.Asp119Asn | missense_variant, splice_region_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD11B2 | ENST00000326152.6 | c.667G>A | p.Asp223Asn | missense_variant, splice_region_variant | 4/5 | 1 | NM_000196.4 | P1 | |
HSD11B2 | ENST00000567684.2 | n.530G>A | splice_region_variant, non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251138Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135852
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461824Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6AN XY: 727204
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Apparent mineralocorticoid excess Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2003 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 27, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 223 of the HSD11B2 protein (p.Asp223Asn). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects HSD11B2 function (PMID: 12788846). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 12101). This variant is also known as 7375 GAC > AAC. This missense change has been observed in individual(s) with clinical features of apparent mineralocorticoid excess (PMID: 12788846). This variant is present in population databases (rs121917833, gnomAD 0.03%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at