rs762100685
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001374736.1(DST):āc.4851A>Gā(p.Arg1617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,612,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
DST
NM_001374736.1 synonymous
NM_001374736.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.33
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 6-56624608-T-C is Benign according to our data. Variant chr6-56624608-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474519.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.33 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001374736.1 | c.4851A>G | p.Arg1617= | synonymous_variant | 36/104 | ENST00000680361.1 | |
DST | NM_001723.7 | c.3240A>G | p.Arg1080= | synonymous_variant | 22/24 | ENST00000370765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000680361.1 | c.4851A>G | p.Arg1617= | synonymous_variant | 36/104 | NM_001374736.1 | |||
DST | ENST00000370765.11 | c.3240A>G | p.Arg1080= | synonymous_variant | 22/24 | 1 | NM_001723.7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000140 AC: 35AN: 250802Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135554
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1460728Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 726732
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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