rs2359681

Variant names:

• chr2-206701216-C-T
• rs2359681
• NM_001093730.1:c.484-1000G>A

Variant summary

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

The NM_001093730.1(DYTN):​c.484-1000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,188 control chromosomes in the GnomAD database, including 1,573 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 0.13 (1573 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DYTN NM_001093730.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 5 publications found

Genes affected

DYTN (HGNC:23279): (dystrotelin) This gene belongs to the dystrophin superfamily, which is characterized by the presence of four EF-hand motifs and a ZZ-domain. It is a likely ortholog of the Drosophila 'discontinuous actin hexagon' gene. It is noteworthy that the coding region of this gene lacks two coding exons that are found in the mouse ortholog. Human transcripts including these two exons are subject to nonsense-mediated transcript decay (NMD). On the other hand, transcripts skipping the two coding exons are expressed at very low levels. While this gene maintains an intact CDS, it may be an evolving pseudogene. However, after a discussion about this gene within the RefSeq group, as well as in the consensus coding sequence (CCDS) collaboration, it was decided to keep it as a protein-coding gene in the RefSeq, Ensembl-GENCODE and the CCDS sets. [provided by RefSeq, Jul 2019]

Y_RNA (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093730.1. 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
	DYTN	NM_001093730.1	MANE Select	c.484-1000G>A		intron	N/A	NP_001087199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYTN	ENST00000452335.2	TSL:1 MANE Select	c.484-1000G>A		intron	N/A	ENSP00000396593.2
	DYTN	ENST00000477734.2	TSL:5	n.*126-1000G>A		intron	N/A	ENSP00000499411.1
	DYTN	ENST00000674258.1		n.795-1000G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19166 AN: 152070 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.135

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.126 AC: 19168 AN: 152188 Hom.: 1573 Cov.: 32 AF XY: 0.127 AC XY: 9431 AN XY: 74402

African (AFR) AF: 0.0304 AC: 1265 AN: 41552

American (AMR) AF: 0.128 AC: 1958 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5180

South Asian (SAS) AF: 0.158 AC: 760 AN: 4810

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10594

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10698 AN: 67988

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.150 Hom.: 1409

Bravo AF: 0.119

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.65
PhyloP100		-0.22
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: rs2359681; hg19: chr2-207565940;