chr2-206707672-C-A

Position:

• chr2-206707672-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

DYTN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYTN	NM_001093730.1	c.95-169G>T		intron_variant		ENST00000452335.2	NP_001087199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYTN	ENST00000452335.2	c.95-169G>T		intron_variant		1	NM_001093730.1	ENSP00000396593.2
DYTN	ENST00000674258.1	n.406-169G>T		intron_variant

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.308

Alfa AF: 0.304 Hom.: 8324

Bravo AF: 0.320

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.56

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: rs10490747; hg19: chr2-207572396;