Genetic Variant DACH1:p.Gly79_Gly81dup (chr13-71866526-T-TGCCGCCGCC) – 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.235_243dupGGCGGCGGC(p.Gly79_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 0.00113 in 1,233,868 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 6)

Exomes 𝑓: 0.00083 ( 5 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

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000826 (901/1090258) while in subpopulation EAS AF = 0.0224 (552/24664). AF 95% confidence interval is 0.0208. There are 5 homozygotes in GnomAdExome4. There are 441 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 494 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.235_243dupGGCGGCGGC	p.Gly79_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.235_243dupGGCGGCGGC	p.Gly79_Gly81dup	conservative_inframe_insertion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1	Q9UI36-2
DACH1	ENST00000619232.2 link	c.235_243dupGGCGGCGGC	p.Gly79_Gly81dup	conservative_inframe_insertion	Exon 1 of 12	5		ENSP00000482797.1	Q9UI36-1
DACH1	ENST00000706274.1 link	c.-225_-217dupGGCGGCGGC		upstream_gene_variant				ENSP00000516320.1	A0A994J7Q8

Frequencies

GnomAD3 genomes

AF:

0.00340

AC:

488

AN:

143518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0165

Gnomad SAS

AF:

0.000442

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000918

Gnomad OTH

AF:

0.00309

GnomAD4 exome

AF:

0.000826

AC:

901

AN:

1090258

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

441

AN XY:

521338

show subpopulations

African (AFR)

AF:

0.0102

AC:

217

AN:

21282

American (AMR)

AF:

0.000124

AC:

AN:

8096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13908

East Asian (EAS)

AF:

0.0224

AC:

552

AN:

24664

South Asian (SAS)

AF:

0.000393

AC:

AN:

20340

European-Finnish (FIN)

AF:

0.0000349

AC:

AN:

28690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2960

European-Non Finnish (NFE)

AF:

0.0000453

AC:

AN:

927192

Other (OTH)

AF:

0.00186

AC:

AN:

43126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00344

AC:

494

AN:

143610

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

253

AN XY:

69844

show subpopulations

African (AFR)

AF:

0.00980

AC:

383

AN:

39072

American (AMR)

AF:

0.00124

AC:

AN:

14566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.0167

AC:

AN:

4718

South Asian (SAS)

AF:

0.000442

AC:

AN:

4528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000918

AC:

AN:

65334

Other (OTH)

AF:

0.00306

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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

Splicing

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

Publications

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13-71866526-TGCCGCCGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCCGCC

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