rs763554

Variant names:

• chrX-86562417-A-G
• rs763554
• NM_053281.3:c.640+48026A>G

Variant summary

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

The NM_053281.3(DACH2):​c.640+48026A>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 0.59 (14539 hom., 18541 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 1 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH2	NM_053281.3	c.640+48026A>G		intron_variant	Intron 3 of 11	ENST00000373125.9	NP_444511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH2	ENST00000373125.9	c.640+48026A>G		intron_variant	Intron 3 of 11	1	NM_053281.3	ENSP00000362217.4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 64455 AN: 109798 Hom.: 14540 Cov.: 23

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.557

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: 0.587 AC: 64499 AN: 109848 Hom.: 14539 Cov.: 23 AF XY: 0.574 AC XY: 18541 AN XY: 32316

African (AFR) AF: 0.815 AC: 24656 AN: 30267

American (AMR) AF: 0.423 AC: 4319 AN: 10213

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1320 AN: 2627

East Asian (EAS) AF: 0.542 AC: 1862 AN: 3433

South Asian (SAS) AF: 0.453 AC: 1201 AN: 2654

European-Finnish (FIN) AF: 0.577 AC: 3353 AN: 5813

Middle Eastern (MID) AF: 0.581 AC: 125 AN: 215

European-Non Finnish (NFE) AF: 0.507 AC: 26623 AN: 52463

Other (OTH) AF: 0.556 AC: 830 AN: 1492

Alfa AF: 0.554 Hom.: 4684

Bravo AF: 0.590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		0.28
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

Other links and lift over

dbSNP: rs763554; hg19: chrX-85817420;