Variant rs2230864 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.5055T>C(p.Asn1685=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,614,172 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 232 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 185 hom. )

Consequence

DST
NM_001723.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.147

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=-0.85).

BP6

Variant 6-56618979-A-G is Benign according to our data. Variant chr6-56618979-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 357568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-56618979-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.147 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0997 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.5055T>C	p.Asn1685=	synonymous_variant	23/24	ENST00000370765.11
DST	NM_001374736.1 linkuse as main transcript	c.4930-4495T>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.5055T>C	p.Asn1685=	synonymous_variant	23/24	1	NM_001723.7		Q03001-3
DST	ENST00000680361.1 linkuse as main transcript	c.4930-4495T>C		intron_variant			NM_001374736.1

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4526

AN:

152180

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.00780

AC:

1959

AN:

251114

Hom.:

AF XY:

0.00570

AC XY:

774

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00306

AC:

4470

AN:

1461874

Hom.:

185

Cov.:

AF XY:

0.00257

AC XY:

1871

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.00709

GnomAD4 genome

AF:

0.0298

AC:

4532

AN:

152298

Hom.:

232

Cov.:

AF XY:

0.0286

AC XY:

2132

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.0000593

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 29, 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

-0.85

CADD

Benign

0.13

DANN

Benign

0.31

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