Variant 13-71488991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_080759.6(DACH1):c.1722+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,611,052 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 54 hom. )

Consequence

DACH1
NM_080759.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.00006060

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.582

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 13-71488991-G-A is Benign according to our data. Variant chr13-71488991-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218830.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACH1	NM_080759.6 linkuse as main transcript	c.1722+6C>T		splice_donor_region_variant, intron_variant		ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5 linkuse as main transcript	c.1722+6C>T	splice_donor_region_variant, intron_variant	1	NM_080759.6	ENSP00000482245	P2	Q9UI36-2
DACH1	ENST00000619232.2 linkuse as main transcript	c.1878+6C>T	splice_donor_region_variant, intron_variant	5		ENSP00000482797	A2	Q9UI36-1
DACH1	ENST00000706274.1 linkuse as main transcript	c.1103+6C>T	splice_donor_region_variant, intron_variant			ENSP00000516320
DACH1	ENST00000706275.1 linkuse as main transcript	c.699+6C>T	splice_donor_region_variant, intron_variant			ENSP00000516321

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

754

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000847

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00806

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00478

AC:

1176

AN:

246232

Hom.:

AF XY:

0.00455

AC XY:

608

AN XY:

133586

show subpopulations

Gnomad AFR exome

AF:

0.000649

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00163

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000796

Gnomad FIN exome

AF:

0.00855

Gnomad NFE exome

AF:

0.00771

Gnomad OTH exome

AF:

0.00438

GnomAD4 exome

AF:

0.00630

AC:

9199

AN:

1459124

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

4552

AN XY:

725806

show subpopulations

Gnomad4 AFR exome

AF:

0.000390

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.00189

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000769

Gnomad4 FIN exome

AF:

0.00840

Gnomad4 NFE exome

AF:

0.00743

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00496

AC:

754

AN:

151928

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

364

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000844

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.00806

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00613

Hom.:

Bravo

AF:

0.00380

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00684

EpiControl

AF:

0.00507

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Oct 02, 2015

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DACH1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.2

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.016

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over