rs149007397
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001723.7(DST):āc.6582A>Cā(p.Ala2194Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,613,858 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0011 ( 0 hom., cov: 32)
Exomes š: 0.00038 ( 3 hom. )
Consequence
DST
NM_001723.7 synonymous
NM_001723.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.28
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 6-56616885-T-G is Benign according to our data. Variant chr6-56616885-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 357556.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.28 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00108 (165/152328) while in subpopulation AFR AF= 0.00253 (105/41566). AF 95% confidence interval is 0.00213. There are 0 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DST | ENST00000370765.11 | c.6582A>C | p.Ala2194Ala | synonymous_variant | Exon 24 of 24 | 1 | NM_001723.7 | ENSP00000359801.6 | ||
| DST | ENST00000680361.1 | c.4930-2401A>C | intron_variant | Intron 36 of 103 | NM_001374736.1 | ENSP00000505098.1 |
Frequencies
GnomAD3 genomes 0.00108 AC: 164AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000663 AC: 166AN: 250374Hom.: 2 AF XY: 0.000620 AC XY: 84AN XY: 135418
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GnomAD4 exome AF: 0.000385 AC: 562AN: 1461530Hom.: 3 Cov.: 34 AF XY: 0.000409 AC XY: 297AN XY: 727048
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GnomAD4 genome 0.00108 AC: 165AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74472
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 6 Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
Dec 10, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
Apr 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
DST: BP4, BP7 -
DST-related disorder Benign:1
Feb 18, 2020
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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
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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