Variant X-86714707-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_053281.3(DACH2):c.1091C>T(p.Thr364Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,172,094 control chromosomes in the GnomAD database, including 1 homozygotes. There are 379 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 1 hom. 371 hem. )

Consequence

DACH2
NM_053281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

Variant links:

Genes affected

DACH2 (HGNC:16814): (dachshund family transcription factor 2) This gene is one of two genes which encode a protein similar to the Drosophila protein dachshund, a transcription factor involved in cell fate determination in the eye, limb and genital disc of the fly. The encoded protein contains two characteristic dachshund domains: an N-terminal domain responsible for DNA binding and a C-terminal domain responsible for protein-protein interactions. This gene is located on the X chromosome and is subject to inactivation by DNA methylation. The encoded protein may be involved in regulation of organogenesis and myogenesis, and may play a role in premature ovarian failure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

DACH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08111212).

BS2

High Hemizygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH2	NM_053281.3 linkuse as main transcript	c.1091C>T	p.Thr364Ile	missense_variant	6/12	ENST00000373125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH2	ENST00000373125.9 linkuse as main transcript	c.1091C>T	p.Thr364Ile	missense_variant	6/12	1	NM_053281.3	A2	Q96NX9-1

Frequencies

GnomAD3 genomes

AF:

0.000411

AC:

AN:

111905

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

34097

show subpopulations

Gnomad AFR

AF:

0.000195

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:

0.000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000249

AC:

AN:

168595

Hom.:

AF XY:

0.000254

AC XY:

AN XY:

55061

show subpopulations

Gnomad AFR exome

AF:

0.000401

Gnomad AMR exome

AF:

0.0000818

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000443

Gnomad OTH exome

AF:

0.000246

GnomAD4 exome

AF:

0.00109

AC:

1159

AN:

1060136

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

371

AN XY:

335612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000778

Gnomad4 AMR exome

AF:

0.0000298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000520

GnomAD4 genome

AF:

0.000411

AC:

AN:

111958

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

AN XY:

34160

show subpopulations

Gnomad4 AFR

AF:

0.000194

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000620

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.1091C>T (p.T364I) alteration is located in exon 6 (coding exon 6) of the DACH2 gene. This alteration results from a C to T substitution at nucleotide position 1091, causing the threonine (T) at amino acid position 364 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.081

T;T;T;T;T;T

MetaSVM

Benign

-0.40

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;N;D;N;.;N

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D;D;D;.;D

Sift4G

Benign

0.072

T;T;D;D;D;T

Polyphen

0.083

B;B;.;.;.;.

Vest4

0.16

MVP

0.64

MPC

0.15

ClinPred

0.076

GERP RS

4.2

Varity_R

0.21

gMVP

0.34

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

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