Variant X-86812876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_053281.3(DACH2):c.1261C>T(p.Pro421Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000418 in 1,195,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 4 hem., cov: 21)

Exomes 𝑓: 0.000022 ( 0 hom. 6 hem. )

Consequence

DACH2
NM_053281.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.30

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1886057).

BP6

Variant X-86812876-C-T is Benign according to our data. Variant chrX-86812876-C-T is described in ClinVar as [Benign]. Clinvar id is 208891.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH2	NM_053281.3 linkuse as main transcript	c.1261C>T	p.Pro421Ser	missense_variant	8/12	ENST00000373125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH2	ENST00000373125.9 linkuse as main transcript	c.1261C>T	p.Pro421Ser	missense_variant	8/12	1	NM_053281.3	A2	Q96NX9-1

Frequencies

GnomAD3 genomes

AF:

0.000235

AC:

AN:

110844

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

33064

show subpopulations

Gnomad AFR

AF:

0.000787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000970

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:

0.00

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.0000719

AC:

AN:

166831

Hom.:

AF XY:

0.0000743

AC XY:

AN XY:

53815

show subpopulations

Gnomad AFR exome

AF:

0.000637

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000320

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1084688

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

352972

show subpopulations

Gnomad4 AFR exome

AF:

0.000619

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.0000440

GnomAD4 genome

AF:

0.000235

AC:

AN:

110844

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

33064

show subpopulations

Gnomad4 AFR

AF:

0.000787

Gnomad4 AMR

AF:

0.0000970

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000272

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Abnormality of neuronal migration

Benign:1

Benign, no assertion criteria provided

clinical testing

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Oct 31, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

1.0

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.85

T;T;T;T;T;T

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Uncertain

-0.26

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

D;D;D;D;.;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.027

D;D;D;D;.;D

Sift4G

Benign

0.094

T;T;T;D;T;D

Polyphen

0.084

B;B;.;.;.;.

Vest4

0.23

MVP

0.66

MPC

0.37

ClinPred

0.18

GERP RS

4.0

Varity_R

0.45

gMVP

0.49

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