chr2-206702398-A-T

Variant names:

• chr2-206702398-A-T
• rs2163033
• NM_001093730.1:c.484-2182T>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001093730.1(DYTN):​c.484-2182T>A variant causes a intron change. The variant allele was found at a frequency of 0.27 in 152,218 control chromosomes in the GnomAD database, including 5,844 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 0.27 (5844 hom., cov: 33)
• Consequence: DYTN NM_001093730.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 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.484-2182T>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.484-2182T>A		intron	N/A	ENSP00000396593.2
	DYTN	ENST00000477734.2	TSL:5	n.*126-2182T>A		intron	N/A	ENSP00000499411.1
	DYTN	ENST00000674258.1		n.795-2182T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41145 AN: 152100 Hom.: 5837 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.270 AC: 41159 AN: 152218 Hom.: 5844 Cov.: 33 AF XY: 0.275 AC XY: 20447 AN XY: 74430

African (AFR) AF: 0.192 AC: 7969 AN: 41534

American (AMR) AF: 0.280 AC: 4278 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2209 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1585 AN: 4828

European-Finnish (FIN) AF: 0.333 AC: 3525 AN: 10584

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19212 AN: 68008

Other (OTH) AF: 0.265 AC: 560 AN: 2114

Alfa AF: 0.146 Hom.: 258

Bravo AF: 0.264

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Benign	0.89
PhyloP100		3.6
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: rs2163033; hg19: chr2-207567122;