chrX-86714707-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_053281.3(DACH2):c.1091C>T(p.Thr364Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,172,094 control chromosomes in the GnomAD database, including 1 homozygotes. There are 379 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., 8 hem., cov: 23)
Exomes 𝑓: 0.0011 ( 1 hom. 371 hem. )
Consequence
DACH2
NM_053281.3 missense
NM_053281.3 missense
Scores
5
10
Clinical Significance
Conservation
PhyloP100: 5.36
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08111212).
BS2
?
High Hemizygotes in GnomAd at 8 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DACH2 | NM_053281.3 | c.1091C>T | p.Thr364Ile | missense_variant | 6/12 | ENST00000373125.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DACH2 | ENST00000373125.9 | c.1091C>T | p.Thr364Ile | missense_variant | 6/12 | 1 | NM_053281.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000411 AC: 46AN: 111905Hom.: 0 Cov.: 23 AF XY: 0.000235 AC XY: 8AN XY: 34097
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GnomAD3 exomes AF: 0.000249 AC: 42AN: 168595Hom.: 0 AF XY: 0.000254 AC XY: 14AN XY: 55061
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GnomAD4 exome AF: 0.00109 AC: 1159AN: 1060136Hom.: 1 Cov.: 29 AF XY: 0.00111 AC XY: 371AN XY: 335612
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GnomAD4 genome ? AF: 0.000411 AC: 46AN: 111958Hom.: 0 Cov.: 23 AF XY: 0.000234 AC XY: 8AN XY: 34160
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.1091C>T (p.T364I) alteration is located in exon 6 (coding exon 6) of the DACH2 gene. This alteration results from a C to T substitution at nucleotide position 1091, causing the threonine (T) at amino acid position 364 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;N;.;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;.;D
Sift4G
Benign
T;T;D;D;D;T
Polyphen
B;B;.;.;.;.
Vest4
MVP
MPC
0.15
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at