13-71866526-TGCCGCCGCC-T

Variant names:

• chr13-71866526-TGCCGCCGCC-T
• rs748058171
• NM_080759.6:c.235_243delGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_080759.6(DACH1):​c.235_243delGGCGGCGGC​(p.Gly79_Gly81del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,233,878 control chromosomes in the GnomAD database, including 1,382 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (153 hom., cov: 6)
  • Exomes 𝑓: 0.044 (1229 hom.)
• Consequence: DACH1 NM_080759.6 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32
• Publications: 2 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_080759.6
• BP6: Variant 13-71866526-TGCCGCCGCC-T is Benign according to our data. Variant chr13-71866526-TGCCGCCGCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1291517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6	c.235_243delGGCGGCGGC	p.Gly79_Gly81del	conservative_inframe_deletion	Exon 1 of 11	ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5	c.235_243delGGCGGCGGC	p.Gly79_Gly81del	conservative_inframe_deletion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1
DACH1	ENST00000619232.2	c.235_243delGGCGGCGGC	p.Gly79_Gly81del	conservative_inframe_deletion	Exon 1 of 12	5		ENSP00000482797.1
DACH1	ENST00000706274.1	c.-225_-217delGGCGGCGGC		upstream_gene_variant				ENSP00000516320.1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5353 AN: 143504 Hom.: 153 Cov.: 6

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0977

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.000211

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0993

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0433

GnomAD4 exome AF: 0.0444 AC: 48451 AN: 1090282 Hom.: 1229 AF XY: 0.0451 AC XY: 23508 AN XY: 521336

African (AFR) AF: 0.00799 AC: 170 AN: 21288

American (AMR) AF: 0.0309 AC: 250 AN: 8096

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 1685 AN: 13908

East Asian (EAS) AF: 0.000202 AC: 5 AN: 24716

South Asian (SAS) AF: 0.0169 AC: 343 AN: 20340

European-Finnish (FIN) AF: 0.0456 AC: 1309 AN: 28678

Middle Eastern (MID) AF: 0.0778 AC: 230 AN: 2958

European-Non Finnish (NFE) AF: 0.0458 AC: 42468 AN: 927168

Other (OTH) AF: 0.0462 AC: 1991 AN: 43130

GnomAD4 genome AF: 0.0373 AC: 5350 AN: 143596 Hom.: 153 Cov.: 6 AF XY: 0.0362 AC XY: 2526 AN XY: 69834

African (AFR) AF: 0.0102 AC: 399 AN: 39080

American (AMR) AF: 0.0374 AC: 545 AN: 14562

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 421 AN: 3386

East Asian (EAS) AF: 0.000212 AC: 1 AN: 4718

South Asian (SAS) AF: 0.0150 AC: 68 AN: 4528

European-Finnish (FIN) AF: 0.0524 AC: 465 AN: 8880

Middle Eastern (MID) AF: 0.100 AC: 28 AN: 280

European-Non Finnish (NFE) AF: 0.0498 AC: 3253 AN: 65322

Other (OTH) AF: 0.0429 AC: 84 AN: 1960

Alfa AF: 0.00 Hom.: 53

Bravo AF: 0.0349

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 25, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=200/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748058171; hg19: chr13-72440658;