Genetic Variant DACH1:p.Gly78_Gly81del (chr13-71866526-TGCCGCCGCCGCC-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_080759.6(DACH1):c.232_243delGGCGGCGGCGGC(p.Gly78_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 0.0000332 in 1,233,914 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.000049 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000031 ( 1 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: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_080759.6

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH1	NM_080759.6 link	c.232_243delGGCGGCGGCGGC	p.Gly78_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.232_243delGGCGGCGGCGGC	p.Gly78_Gly81del	conservative_inframe_deletion	Exon 1 of 11	1	NM_080759.6	ENSP00000482245.1	Q9UI36-2
DACH1	ENST00000619232.2 link	c.232_243delGGCGGCGGCGGC	p.Gly78_Gly81del	conservative_inframe_deletion	Exon 1 of 12	5		ENSP00000482797.1	Q9UI36-1
DACH1	ENST00000706274.1 link	c.-228_-217delGGCGGCGGCGGC		upstream_gene_variant				ENSP00000516320.1	A0A994J7Q8

Frequencies

GnomAD3 genomes

AF:

0.0000488

AC:

AN:

143522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000128

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:

0.0000306

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000312

AC:

AN:

1090300

Hom.:

AF XY:

0.0000269

AC XY:

AN XY:

521346

show subpopulations

African (AFR)

AF:

0.000141

AC:

AN:

21288

American (AMR)

AF:

0.000124

AC:

AN:

8096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13906

East Asian (EAS)

AF:

0.00

AC:

AN:

24716

South Asian (SAS)

AF:

0.0000983

AC:

AN:

20340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28688

Middle Eastern (MID)

AF:

0.00101

AC:

AN:

2960

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

927178

Other (OTH)

AF:

0.00

AC:

AN:

43128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000487

AC:

AN:

143614

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

69844

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

39078

American (AMR)

AF:

0.00

AC:

AN:

14566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

4718

South Asian (SAS)

AF:

0.00

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:

0.0000306

AC:

AN:

65332

Other (OTH)

AF:

0.00

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

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

Mutation Taster

=199/1

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-TGCCGCC

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