rs6906792

Variant names:

• chr6-56538978-T-G
• rs6906792
• NM_001374736.1:c.16609-2038A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374736.1(DST):​c.16609-2038A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,914 control chromosomes in the GnomAD database, including 33,456 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33456 hom., cov: 31)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• hereditary sensory and autonomic neuropathy type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374736.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	NM_001374736.1	MANE Select	c.16609-2038A>C		intron	N/A	NP_001361665.1
	DST	NM_001374734.1		c.16636-2038A>C		intron	N/A	NP_001361663.1
	DST	NM_001374722.1		c.16609-2038A>C		intron	N/A	NP_001361651.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DST	ENST00000680361.1	MANE Select	c.16609-2038A>C		intron	N/A	ENSP00000505098.1
	DST	ENST00000244364.10	TSL:1	c.8740-2038A>C		intron	N/A	ENSP00000244364.6
	DST	ENST00000361203.7	TSL:5	c.15976-2038A>C		intron	N/A	ENSP00000354508.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99887 AN: 151794 Hom.: 33427 Cov.: 31

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.623

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.658 AC: 99966 AN: 151914 Hom.: 33456 Cov.: 31 AF XY: 0.662 AC XY: 49148 AN XY: 74260

African (AFR) AF: 0.545 AC: 22548 AN: 41400

American (AMR) AF: 0.672 AC: 10268 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3431 AN: 5164

South Asian (SAS) AF: 0.656 AC: 3150 AN: 4802

European-Finnish (FIN) AF: 0.818 AC: 8650 AN: 10574

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47895 AN: 67922

Other (OTH) AF: 0.625 AC: 1314 AN: 2102

Alfa AF: 0.679 Hom.: 4589

Bravo AF: 0.640

Asia WGS AF: 0.655 AC: 2275 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.57
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6906792; hg19: chr6-56403776;