chr6-56517114-G-A

Position:

• chr6-56517114-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374736.1(DST):​c.18357+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 960,358 control chromosomes in the GnomAD database, including 232,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33426 hom., cov: 31)
  • Exomes 𝑓: 0.70 (198960 hom.)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.958

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-56517114-G-A is Benign according to our data. Variant chr6-56517114-G-A is described in ClinVar as [Benign]. Clinvar id is 1288855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DST	NM_001374736.1	c.18357+84C>T		intron_variant		ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1	c.18357+84C>T		intron_variant			NM_001374736.1	ENSP00000505098.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99903 AN: 151832 Hom.: 33400 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.626

GnomAD4 exome AF: 0.699 AC: 565124 AN: 808408 Hom.: 198960 AF XY: 0.698 AC XY: 297910 AN XY: 426978

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.658 AC: 99976 AN: 151950 Hom.: 33426 Cov.: 31 AF XY: 0.662 AC XY: 49163 AN XY: 74272

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.629

Alfa AF: 0.682 Hom.: 7985

Bravo AF: 0.640

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.76
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs4715626; hg19: chr6-56381912;