Genetic Variant DACH1:p.Gly81del (chr13-71866526-TGCC-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_080759.6(DACH1):c.241_243delGGC(p.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 0.00222 in 1,221,546 control chromosomes in the GnomAD database, including 26 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0087 ( 18 hom., cov: 6)

Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

DACH1
NM_080759.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

2 publications found

Variant links:

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]

DACH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_080759.6

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00866 (1244/143598) while in subpopulation AFR AF = 0.0299 (1169/39078). AF 95% confidence interval is 0.0285. There are 18 homozygotes in GnomAd4. There are 595 alleles in the male GnomAd4 subpopulation. Median coverage is 6. This position passed quality control check.

BS2

High AC in GnomAd4 at 1244 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.241_243delGGC	p.Gly81del	conservative_inframe_deletion	Exon 1 of 11	ENST00000613252.5	NP_542937.3	Q9UI36-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DACH1	ENST00000613252.5 link	c.241_243delGGC	p.Gly81del	conservative_inframe_deletion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1	Q9UI36-2
DACH1	ENST00000619232.2 link	c.241_243delGGC	p.Gly81del	conservative_inframe_deletion	Exon 1 of 12	5		ENSP00000482797.1	Q9UI36-1
DACH1	ENST00000706274.1 link	c.-219_-217delGGC		upstream_gene_variant				ENSP00000516320.1	A0A994J7Q8

Frequencies

GnomAD3 genomes

AF:

0.00866

AC:

1243

AN:

143506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00296

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000634

Gnomad SAS

AF:

0.000883

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000199

Gnomad OTH

AF:

0.00619

GnomAD4 exome

AF:

0.00136

AC:

1467

AN:

1077948

Hom.:

AF XY:

0.00147

AC XY:

755

AN XY:

515050

show subpopulations

African (AFR)

AF:

0.0319

AC:

676

AN:

21166

American (AMR)

AF:

0.00381

AC:

AN:

7878

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

13624

East Asian (EAS)

AF:

0.00136

AC:

AN:

24350

South Asian (SAS)

AF:

0.00119

AC:

AN:

20160

European-Finnish (FIN)

AF:

0.00212

AC:

AN:

27786

Middle Eastern (MID)

AF:

0.00172

AC:

AN:

2902

European-Non Finnish (NFE)

AF:

0.000548

AC:

503

AN:

917568

Other (OTH)

AF:

0.00282

AC:

120

AN:

42514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00866

AC:

1244

AN:

143598

Hom.:

Cov.:

AF XY:

0.00852

AC XY:

595

AN XY:

69838

show subpopulations

African (AFR)

AF:

0.0299

AC:

1169

AN:

39078

American (AMR)

AF:

0.00295

AC:

AN:

14558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.000636

AC:

AN:

4718

South Asian (SAS)

AF:

0.000883

AC:

AN:

4528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000199

AC:

AN:

65326

Other (OTH)

AF:

0.00612

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over