rs6704787

Positions:

• chr2-206691024-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000452335.2(DYTN):​c.980+2151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,200 control chromosomes in the GnomAD database, including 2,369 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 0.12 (2369 hom., cov: 32)
• Consequence: DYTN ENST00000452335.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYTN	NM_001093730.1	c.980+2151T>C		intron_variant		ENST00000452335.2	NP_001087199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYTN	ENST00000452335.2	c.980+2151T>C		intron_variant		1	NM_001093730.1	ENSP00000396593	P1
DYTN	ENST00000674258.1	n.1291+2151T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18459 AN: 152082 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.122 AC: 18525 AN: 152200 Hom.: 2369 Cov.: 32 AF XY: 0.117 AC XY: 8690 AN XY: 74442

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0475

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0748 Hom.: 199

Bravo AF: 0.135

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.7
DANN	Benign	0.36

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: rs6704787; hg19: chr2-207555748;