chrX-86812948-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_053281.3(DACH2):c.1333C>T(p.Pro445Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,403 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
DACH2
NM_053281.3 missense
NM_053281.3 missense
Scores
1
7
7
Clinical Significance
Conservation
PhyloP100: 3.47
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DACH2 | NM_053281.3 | c.1333C>T | p.Pro445Ser | missense_variant | 8/12 | ENST00000373125.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DACH2 | ENST00000373125.9 | c.1333C>T | p.Pro445Ser | missense_variant | 8/12 | 1 | NM_053281.3 | A2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
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22
GnomAD3 exomes AF: 0.00000560 AC: 1AN: 178564Hom.: 0 AF XY: 0.0000158 AC XY: 1AN XY: 63264
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GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095403Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 360883
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GnomAD4 genome Cov.: 22
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22
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 | Apr 12, 2022 | The c.1333C>T (p.P445S) alteration is located in exon 8 (coding exon 8) of the DACH2 gene. This alteration results from a C to T substitution at nucleotide position 1333, causing the proline (P) at amino acid position 445 to be replaced by a serine (S). 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
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;.;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;.;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
P;P;.;.;.;.
Vest4
MutPred
0.62
.;Gain of catalytic residue at P445 (P = 0.0405);.;.;.;.;
MVP
MPC
0.17
ClinPred
D
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