rs12164321

Variant names:

• chrX-86624851-T-C
• rs12164321
• NM_053281.3:c.641-26185T>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.641-26185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 110,924 control chromosomes in the GnomAD database, including 1,016 homozygotes. There are 4,831 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 0.14 (1016 hom., 4831 hem., cov: 22)
• Consequence: DACH2 NM_053281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACH2	NM_053281.3	c.641-26185T>C		intron_variant	Intron 3 of 11	ENST00000373125.9	NP_444511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACH2	ENST00000373125.9	c.641-26185T>C		intron_variant	Intron 3 of 11	1	NM_053281.3	ENSP00000362217.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15965 AN: 110871 Hom.: 1017 Cov.: 22

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0585

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.144 AC: 15960 AN: 110924 Hom.: 1016 Cov.: 22 AF XY: 0.146 AC XY: 4831 AN XY: 33136

African (AFR) AF: 0.0606 AC: 1855 AN: 30589

American (AMR) AF: 0.126 AC: 1309 AN: 10420

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 359 AN: 2645

East Asian (EAS) AF: 0.313 AC: 1083 AN: 3459

South Asian (SAS) AF: 0.357 AC: 924 AN: 2587

European-Finnish (FIN) AF: 0.240 AC: 1411 AN: 5890

Middle Eastern (MID) AF: 0.144 AC: 31 AN: 216

European-Non Finnish (NFE) AF: 0.165 AC: 8737 AN: 52926

Other (OTH) AF: 0.140 AC: 211 AN: 1508

Alfa AF: 0.167 Hom.: 4948

Bravo AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-0.34
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: rs12164321; hg19: chrX-85879854;