Variant rs2230863 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001723.7(DST):c.4980A>C(p.Val1660=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,614,152 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 212 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 255 hom. )

Consequence

DST
NM_001723.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.35

Variant links:

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]

DST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 6-56619054-T-G is Benign according to our data. Variant chr6-56619054-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 357569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-56619054-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DST	NM_001723.7 linkuse as main transcript	c.4980A>C	p.Val1660=	synonymous_variant	23/24	ENST00000370765.11
DST	NM_001374736.1 linkuse as main transcript	c.4930-4570A>C		intron_variant		ENST00000680361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DST	ENST00000370765.11 linkuse as main transcript	c.4980A>C	p.Val1660=	synonymous_variant	23/24	1	NM_001723.7		Q03001-3
DST	ENST00000680361.1 linkuse as main transcript	c.4930-4570A>C		intron_variant			NM_001374736.1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4675

AN:

152210

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.0105

AC:

2635

AN:

250924

Hom.:

AF XY:

0.00841

AC XY:

1141

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00892

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0231

Gnomad SAS exome

AF:

0.000785

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000697

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.00423

AC:

6190

AN:

1461824

Hom.:

255

Cov.:

AF XY:

0.00377

AC XY:

2744

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.00979

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0155

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.000433

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.0308

AC:

4693

AN:

152328

Hom.:

212

Cov.:

AF XY:

0.0299

AC XY:

2230

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0358

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2021	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.088

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over