rs143101723
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_001374736.1(DST):c.2042G>A(p.Arg681His) variant causes a missense change. The variant allele was found at a frequency of 0.0004 in 1,614,024 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R681C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001374736.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001374736.1 | c.2042G>A | p.Arg681His | missense_variant | 18/104 | ENST00000680361.1 | |
DST | NM_001723.7 | c.431G>A | p.Arg144His | missense_variant | 4/24 | ENST00000370765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000680361.1 | c.2042G>A | p.Arg681His | missense_variant | 18/104 | NM_001374736.1 | |||
DST | ENST00000370765.11 | c.431G>A | p.Arg144His | missense_variant | 4/24 | 1 | NM_001723.7 |
Frequencies
GnomAD3 genomes AF: 0.000592 AC: 90AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000732 AC: 183AN: 250034Hom.: 0 AF XY: 0.000747 AC XY: 101AN XY: 135240
GnomAD4 exome AF: 0.000380 AC: 556AN: 1461768Hom.: 2 Cov.: 34 AF XY: 0.000400 AC XY: 291AN XY: 727194
GnomAD4 genome AF: 0.000591 AC: 90AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74440
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary sensory and autonomic neuropathy type 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 01, 2019 | This alteration is classified as likely 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. - |
DST-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 13, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at