rs34628660
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001723.7(DST):c.6831C>T(p.Ala2277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,614,030 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 (★★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 0 hom. )
Consequence
DST
NM_001723.7 synonymous
NM_001723.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.276
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 6-56616636-G-A is Benign according to our data. Variant chr6-56616636-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.276 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.6831C>T | p.Ala2277= | synonymous_variant | 24/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.4930-2152C>T | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.6831C>T | p.Ala2277= | synonymous_variant | 24/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.4930-2152C>T | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000167 AC: 42AN: 251292Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135808
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GnomAD4 exome AF: 0.000423 AC: 618AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.000411 AC XY: 299AN XY: 727236
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Jan 15, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | DST: BP4, BP7 - |
Computational scores
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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