2-206707672-C-A

Variant names:

• chr2-206707672-C-A
• rs10490747
• NM_001093730.1:c.95-169G>T

Variant summary

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

The NM_001093730.1(DYTN):​c.95-169G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,902 control chromosomes in the GnomAD database, including 8,078 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 0.32 (8078 hom., cov: 33)
• Consequence: DYTN NM_001093730.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 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.95-169G>T		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.95-169G>T		intron	N/A	ENSP00000396593.2
	DYTN	ENST00000674258.1		n.406-169G>T		intron	N/A
	DYTN	ENST00000477734.2	TSL:5	n.-171G>T		upstream_gene	N/A	ENSP00000499411.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49156 AN: 151786 Hom.: 8070 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.324 AC: 49186 AN: 151902 Hom.: 8078 Cov.: 33 AF XY: 0.327 AC XY: 24285 AN XY: 74230

African (AFR) AF: 0.326 AC: 13490 AN: 41426

American (AMR) AF: 0.310 AC: 4723 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2280 AN: 5166

South Asian (SAS) AF: 0.390 AC: 1870 AN: 4790

European-Finnish (FIN) AF: 0.338 AC: 3565 AN: 10550

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20745 AN: 67934

Other (OTH) AF: 0.308 AC: 648 AN: 2106

Alfa AF: 0.304 Hom.: 9801

Bravo AF: 0.320

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		0.11
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: rs10490747; hg19: chr2-207572396;