rs200851963
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001374736.1(DST):c.2733A>T(p.Thr911Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
DST
NM_001374736.1 synonymous
NM_001374736.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.200
Genes affected
DST (HGNC:1090): (dystonin) This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been reported that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 6-56639576-T-A is Benign according to our data. Variant chr6-56639576-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 390190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.2 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000237 (36/152158) while in subpopulation EAS AF= 0.00696 (36/5176). AF 95% confidence interval is 0.00516. There are 1 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DST | ENST00000680361.1 | c.2733A>T | p.Thr911Thr | synonymous_variant | Exon 21 of 104 | NM_001374736.1 | ENSP00000505098.1 | |||
| DST | ENST00000370765.11 | c.1122A>T | p.Thr374Thr | synonymous_variant | Exon 7 of 24 | 1 | NM_001723.7 | ENSP00000359801.6 |
Frequencies
GnomAD3 genomes 0.000237 AC: 36AN: 152040Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000506 AC: 127AN: 251186Hom.: 0 AF XY: 0.000493 AC XY: 67AN XY: 135766
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GnomAD4 exome AF: 0.000156 AC: 228AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.000142 AC XY: 103AN XY: 727140
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GnomAD4 genome 0.000237 AC: 36AN: 152158Hom.: 1 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74382
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Oct 31, 2016
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at