rs4240068

Positions:

• chrX-86189754-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053281.3(DACH2):​c.488+40646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 110,612 control chromosomes in the GnomAD database, including 7,884 homozygotes. There are 13,183 hemizygotes in GnomAD. 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 0.41 (7884 hom., 13183 hem., cov: 23)
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACH2	NM_053281.3	c.488+40646G>A		intron_variant		ENST00000373125.9	NP_444511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACH2	ENST00000373125.9	c.488+40646G>A		intron_variant		1	NM_053281.3	ENSP00000362217.4
DACH2	ENST00000373131.5	c.488+40646G>A		intron_variant		2		ENSP00000362223.1
DACH2	ENST00000461604.6	n.488+40646G>A		intron_variant		5		ENSP00000421509.1
DACH2	ENST00000506327.6	n.*78+5404G>A		intron_variant		2		ENSP00000426837.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 45870 AN: 110562 Hom.: 7892 Cov.: 23 AF XY: 0.401 AC XY: 13176 AN XY: 32838

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.568

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.415 AC: 45863 AN: 110612 Hom.: 7884 Cov.: 23 AF XY: 0.401 AC XY: 13183 AN XY: 32898

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.435

Alfa AF: 0.464 Hom.: 4042

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.48

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: rs4240068; hg19: chrX-85444758;