Genetic Variant DACH1:p.Gly80_Gly81dup (chr13-71866526-T-TGCCGCC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BA1

The NM_080759.6(DACH1):c.238_243dupGGCGGC(p.Gly80_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 0.132 in 1,231,072 control chromosomes in the GnomAD database, including 15,324 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 6934 hom., cov: 6)

Exomes 𝑓: 0.12 ( 8390 hom. )

Consequence

DACH1
NM_080759.6 conservative_inframe_insertion

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.238_243dupGGCGGC	p.Gly80_Gly81dup	conservative_inframe_insertion	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.238_243dupGGCGGC	p.Gly80_Gly81dup	conservative_inframe_insertion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1	Q9UI36-2
DACH1	ENST00000619232.2 link	c.238_243dupGGCGGC	p.Gly80_Gly81dup	conservative_inframe_insertion	Exon 1 of 12	5		ENSP00000482797.1	Q9UI36-1
DACH1	ENST00000706274.1 link	c.-222_-217dupGGCGGC		upstream_gene_variant				ENSP00000516320.1	A0A994J7Q8

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

35749

AN:

143330

Hom.:

6917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.117

AC:

127100

AN:

1087650

Hom.:

8390

Cov.:

AF XY:

0.115

AC XY:

59970

AN XY:

519944

show subpopulations

African (AFR)

AF:

0.509

AC:

10765

AN:

21148

American (AMR)

AF:

0.163

AC:

1308

AN:

8008

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

1621

AN:

13812

East Asian (EAS)

AF:

0.388

AC:

9470

AN:

24396

South Asian (SAS)

AF:

0.121

AC:

2456

AN:

20314

European-Finnish (FIN)

AF:

0.0992

AC:

2828

AN:

28498

Middle Eastern (MID)

AF:

0.114

AC:

337

AN:

2948

European-Non Finnish (NFE)

AF:

0.0994

AC:

92030

AN:

925558

Other (OTH)

AF:

0.146

AC:

6285

AN:

42968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

5374

10748

16122

21496

26870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4202

8404

12606

16808

21010

<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:

0.250

AC:

35815

AN:

143422

Hom.:

6934

Cov.:

AF XY:

0.248

AC XY:

17279

AN XY:

69756

show subpopulations

African (AFR)

AF:

0.540

AC:

21052

AN:

38978

American (AMR)

AF:

0.202

AC:

2945

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

455

AN:

3384

East Asian (EAS)

AF:

0.446

AC:

2103

AN:

4712

South Asian (SAS)

AF:

0.138

AC:

626

AN:

4524

European-Finnish (FIN)

AF:

0.107

AC:

948

AN:

8868

Middle Eastern (MID)

AF:

0.139

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.109

AC:

7138

AN:

65282

Other (OTH)

AF:

0.209

AC:

410

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

983

1966

2949

3932

4915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.0161

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=92/8

polymorphism

(source)

Splicing

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

Publications

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13-71866526-TGCCGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCC

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