rs115542549
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001723.7(DST):āc.6633A>Gā(p.Ala2211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 1,614,152 control chromosomes in the GnomAD database, including 1,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.025 ( 76 hom., cov: 32)
Exomes š: 0.040 ( 1418 hom. )
Consequence
DST
NM_001723.7 synonymous
NM_001723.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.712
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 6-56616834-T-C is Benign according to our data. Variant chr6-56616834-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 357555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-56616834-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.712 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0249 (3787/152326) while in subpopulation NFE AF= 0.0417 (2834/68026). AF 95% confidence interval is 0.0404. There are 76 homozygotes in gnomad4. There are 1679 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 76 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DST | NM_001723.7 | c.6633A>G | p.Ala2211= | synonymous_variant | 24/24 | ENST00000370765.11 | |
DST | NM_001374736.1 | c.4930-2350A>G | intron_variant | ENST00000680361.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DST | ENST00000370765.11 | c.6633A>G | p.Ala2211= | synonymous_variant | 24/24 | 1 | NM_001723.7 | ||
DST | ENST00000680361.1 | c.4930-2350A>G | intron_variant | NM_001374736.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0249 AC: 3785AN: 152208Hom.: 75 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3785
AN:
152208
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0251 AC: 6297AN: 251198Hom.: 114 AF XY: 0.0258 AC XY: 3506AN XY: 135778
GnomAD3 exomes
AF:
AC:
6297
AN:
251198
Hom.:
AF XY:
AC XY:
3506
AN XY:
135778
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0398 AC: 58168AN: 1461826Hom.: 1418 Cov.: 34 AF XY: 0.0391 AC XY: 28435AN XY: 727212
GnomAD4 exome
AF:
AC:
58168
AN:
1461826
Hom.:
Cov.:
34
AF XY:
AC XY:
28435
AN XY:
727212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0249 AC: 3787AN: 152326Hom.: 76 Cov.: 32 AF XY: 0.0225 AC XY: 1679AN XY: 74492
GnomAD4 genome
?
AF:
AC:
3787
AN:
152326
Hom.:
Cov.:
32
AF XY:
AC XY:
1679
AN XY:
74492
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
65
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
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
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2021 | - - |
Hereditary sensory and autonomic neuropathy type 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at