rs2078588

Variant names:

• chr13-71727500-C-A
• rs2078588
• NM_080759.6:c.849-45590G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_080759.6(DACH1):​c.849-45590G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,070 control chromosomes in the GnomAD database, including 12,670 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 0.26 (12670 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 6 publications found

Genes affected

DACH1 (HGNC:2663): (dachshund family transcription factor 1) This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6	c.849-45590G>T		intron_variant	Intron 1 of 10	ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5	c.849-45590G>T		intron_variant	Intron 1 of 10	1	NM_080759.6	ENSP00000482245.1
DACH1	ENST00000619232.2	c.849-45590G>T		intron_variant	Intron 1 of 11	5		ENSP00000482797.1
DACH1	ENST00000706274.1	c.390-45590G>T		intron_variant	Intron 1 of 9			ENSP00000516320.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39295 AN: 151950 Hom.: 12616 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.259 AC: 39406 AN: 152070 Hom.: 12670 Cov.: 32 AF XY: 0.254 AC XY: 18878 AN XY: 74358

African (AFR) AF: 0.758 AC: 31443 AN: 41490

American (AMR) AF: 0.149 AC: 2278 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5168

South Asian (SAS) AF: 0.0841 AC: 406 AN: 4826

European-Finnish (FIN) AF: 0.0191 AC: 202 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2858 AN: 67924

Other (OTH) AF: 0.220 AC: 465 AN: 2112

Alfa AF: 0.114 Hom.: 7233

Bravo AF: 0.293

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		2.2
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: rs2078588; hg19: chr13-72301632;