rs5923642

Variant names:

• chrX-86789205-C-T
• rs5923642
• NM_053281.3:c.1241-23651C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH2	NM_053281.3	MANE Select	c.1241-23651C>T		intron	N/A	NP_444511.1
	DACH2	NM_001139514.1		c.1202-23651C>T		intron	N/A	NP_001132986.1
	DACH2	NM_001139515.1		c.740-23651C>T		intron	N/A	NP_001132987.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH2	ENST00000373125.9	TSL:1 MANE Select	c.1241-23651C>T		intron	N/A	ENSP00000362217.4
	DACH2	ENST00000373131.5	TSL:2	c.1202-23651C>T		intron	N/A	ENSP00000362223.1
	DACH2	ENST00000508860.5	TSL:2	c.740-23651C>T		intron	N/A	ENSP00000420896.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 32916 AN: 110828 Hom.: 3842 Cov.: 23

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

African (AFR) AF: 0.250 AC: 7656 AN: 30581

American (AMR) AF: 0.207 AC: 2151 AN: 10411

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1098 AN: 2637

East Asian (EAS) AF: 0.0235 AC: 83 AN: 3526

South Asian (SAS) AF: 0.0938 AC: 251 AN: 2675

European-Finnish (FIN) AF: 0.342 AC: 1999 AN: 5848

Middle Eastern (MID) AF: 0.413 AC: 88 AN: 213

European-Non Finnish (NFE) AF: 0.357 AC: 18871 AN: 52822

Other (OTH) AF: 0.301 AC: 451 AN: 1500

Alfa AF: 0.333 Hom.: 36687

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.65
PhyloP100		0.16
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: rs5923642; hg19: chrX-86044208;