rs5923642

chrX-86789205-C-T

Variant summary

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

The NM_053281.3(DACH2):c.1241-23651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 110,878 control chromosomes in the GnomAD database, including 3,839 homozygotes. There are 9,381 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 0.30 (3839 hom., 9381 hem., cov: 23)
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH2	NM_053281.3	c.1241-23651C>T		intron_variant		ENST00000373125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH2	ENST00000373125.9	c.1241-23651C>T		intron_variant		1	NM_053281.3	A2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 32916 AN: 110828 Hom.: 3842 Cov.: 23 AF XY: 0.283 AC XY: 9364 AN XY: 33080

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.425

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.297 AC: 32915 AN: 110878 Hom.: 3839 Cov.: 23 AF XY: 0.283 AC XY: 9381 AN XY: 33140

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.301

Alfa AF: 0.341 Hom.: 30118

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.8
Dann	Benign	0.65

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: rs5923642; hg19: chrX-86044208;