rs1578826

Variant names:

• chrX-86747453-A-G
• rs1578826
• NM_053281.3:c.1240+7571A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-86747453-A-G
• chrX-86747453-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH2	NM_053281.3	MANE Select	c.1240+7571A>G		intron	N/A	NP_444511.1	Q96NX9-1
	DACH2	NM_001139514.1		c.1201+7571A>G		intron	N/A	NP_001132986.1	A8K3I1
	DACH2	NM_001139515.1		c.739+7571A>G		intron	N/A	NP_001132987.1	Q96NX9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH2	ENST00000373125.9	TSL:1 MANE Select	c.1240+7571A>G		intron	N/A	ENSP00000362217.4	Q96NX9-1
	DACH2	ENST00000373131.5	TSL:2	c.1201+7571A>G		intron	N/A	ENSP00000362223.1	Q96NX9-2
	DACH2	ENST00000508860.5	TSL:2	c.739+7571A>G		intron	N/A	ENSP00000420896.1	Q96NX9-4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 83172 AN: 109562 Hom.: 22886 Cov.: 22

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

African (AFR) AF: 0.832 AC: 25071 AN: 30143

American (AMR) AF: 0.530 AC: 5414 AN: 10207

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2125 AN: 2615

East Asian (EAS) AF: 0.844 AC: 2900 AN: 3436

South Asian (SAS) AF: 0.673 AC: 1697 AN: 2523

European-Finnish (FIN) AF: 0.828 AC: 4730 AN: 5716

Middle Eastern (MID) AF: 0.845 AC: 180 AN: 213

European-Non Finnish (NFE) AF: 0.750 AC: 39470 AN: 52599

Other (OTH) AF: 0.729 AC: 1080 AN: 1481

Alfa AF: 0.743 Hom.: 30480

Bravo AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1578826;

hg19: chrX-86002456;