NM_080759.6:c.223_243dupGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr13-71866526-T-TGCCGCCGCCGCCGCCGCCGCC
• rs748058171
• NM_080759.6:c.223_243dupGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_080759.6(DACH1):​c.223_243dupGGCGGCGGCGGCGGCGGCGGC​(p.Gly75_Gly81dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 143,618 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000070 (0 hom., cov: 6)
• Consequence: DACH1 NM_080759.6 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_080759.6

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6	c.223_243dupGGCGGCGGCGGCGGCGGCGGC	p.Gly75_Gly81dup	conservative_inframe_insertion	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.223_243dupGGCGGCGGCGGCGGCGGCGGC	p.Gly75_Gly81dup	conservative_inframe_insertion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1
DACH1	ENST00000619232.2	c.223_243dupGGCGGCGGCGGCGGCGGCGGC	p.Gly75_Gly81dup	conservative_inframe_insertion	Exon 1 of 12	5		ENSP00000482797.1
DACH1	ENST00000706274.1	c.-237_-217dupGGCGGCGGCGGCGGCGGCGGC		upstream_gene_variant				ENSP00000516320.1

Frequencies

GnomAD3 genomes AF: 0.00000697 AC: 1 AN: 143526 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000696 AC: 1 AN: 143618 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 69848

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000256 AC: 1 AN: 39080

American (AMR) AF: 0.00 AC: 0 AN: 14566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 4718

South Asian (SAS) AF: 0.00 AC: 0 AN: 4528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65334

Other (OTH) AF: 0.00 AC: 0 AN: 1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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;