chrX-86302436-A-G

Variant names:

• chrX-86302436-A-G
• rs6617219
• NM_053281.3:c.489-74388A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053281.3(DACH2):​c.489-74388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 111,122 control chromosomes in the GnomAD database, including 1,372 homozygotes. There are 5,262 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 0.16 (1372 hom., 5262 hem., cov: 22)
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) 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.489-74388A>G		intron_variant	Intron 1 of 11	ENST00000373125.9	NP_444511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH2	ENST00000373125.9	c.489-74388A>G		intron_variant	Intron 1 of 11	1	NM_053281.3	ENSP00000362217.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 17979 AN: 111080 Hom.: 1371 Cov.: 22

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.162 AC: 17975 AN: 111122 Hom.: 1372 Cov.: 22 AF XY: 0.158 AC XY: 5262 AN XY: 33382

African (AFR) AF: 0.0426 AC: 1316 AN: 30866

American (AMR) AF: 0.162 AC: 1685 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 488 AN: 2637

East Asian (EAS) AF: 0.297 AC: 1032 AN: 3474

South Asian (SAS) AF: 0.344 AC: 925 AN: 2692

European-Finnish (FIN) AF: 0.168 AC: 974 AN: 5785

Middle Eastern (MID) AF: 0.210 AC: 45 AN: 214

European-Non Finnish (NFE) AF: 0.209 AC: 11076 AN: 52877

Other (OTH) AF: 0.166 AC: 251 AN: 1516

Alfa AF: 0.187 Hom.: 8062

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.87
DANN	Benign	0.49
PhyloP100		-0.27
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: rs6617219; hg19: chrX-85557439;