rs5968924

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 (AFR) allele frequency at 95% confidence interval = 0.325 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.527+58700T>C		intron	N/A	NP_444511.1
	DACH2	NM_001139514.1		c.489-78717T>C		intron	N/A	NP_001132986.1
	DACH2	NM_001139515.1		c.26+58700T>C		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.527+58700T>C		intron	N/A	ENSP00000362217.4
	DACH2	ENST00000373131.5	TSL:2	c.489-78717T>C		intron	N/A	ENSP00000362223.1
	DACH2	ENST00000508860.5	TSL:2	c.26+58700T>C		intron	N/A	ENSP00000420896.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22779 AN: 111037 Hom.: 2038 Cov.: 23

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

African (AFR) AF: 0.331 AC: 10080 AN: 30481

American (AMR) AF: 0.163 AC: 1706 AN: 10454

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 352 AN: 2640

East Asian (EAS) AF: 0.260 AC: 916 AN: 3519

South Asian (SAS) AF: 0.258 AC: 690 AN: 2670

European-Finnish (FIN) AF: 0.129 AC: 772 AN: 5967

Middle Eastern (MID) AF: 0.121 AC: 26 AN: 214

European-Non Finnish (NFE) AF: 0.150 AC: 7918 AN: 52951

Other (OTH) AF: 0.193 AC: 292 AN: 1513

Alfa AF: 0.172 Hom.: 11056

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		0.75
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: rs5968924; hg19: chrX-85690565;