NM_053281.3:c.527+58700T>C

Variant names:

• chrX-86435562-T-C
• rs5968924
• NM_053281.3:c.527+58700T>C

Variant summary

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

The NM_053281.3(DACH2):​c.527+58700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 111,088 control chromosomes in the GnomAD database, including 2,037 homozygotes. There are 6,428 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 0.21 (2037 hom., 6428 hem., cov: 23)
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH2	NM_053281.3	c.527+58700T>C		intron_variant	Intron 2 of 11	ENST00000373125.9	NP_444511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH2	ENST00000373125.9	c.527+58700T>C		intron_variant	Intron 2 of 11	1	NM_053281.3	ENSP00000362217.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22779 AN: 111037 Hom.: 2038 Cov.: 23 AF XY: 0.193 AC XY: 6414 AN XY: 33297

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0530

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.205 AC: 22788 AN: 111088 Hom.: 2037 Cov.: 23 AF XY: 0.193 AC XY: 6428 AN XY: 33358

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.193

Alfa AF: 0.167 Hom.: 8116

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.55

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: rs5968924; hg19: chrX-85690565;