rs1578826

chrX-86747453-A-GchrX-86747453-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_053281.3(DACH2):c.1240+7571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (22884 hom., 24063 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd at 22886 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH2	NM_053281.3	c.1240+7571A>G		intron_variant		ENST00000373125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH2	ENST00000373125.9	c.1240+7571A>G		intron_variant		1	NM_053281.3	A2

Frequencies

GnomAD3 genomes AF: 0.759 AC: 83172 AN: 109562 Hom.: 22886 Cov.: 22 AF XY: 0.753 AC XY: 24005 AN XY: 31890

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.846

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.730

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.759 AC: 83221 AN: 109610 Hom.: 22884 Cov.: 22 AF XY: 0.753 AC XY: 24063 AN XY: 31948

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.729

Alfa AF: 0.747 Hom.: 20332

Bravo AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs1578826; hg19: chrX-86002456;