chrX-86812876-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_053281.3(DACH2):c.1261C>T(p.Pro421Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000418 in 1,195,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: đť‘“ 0.00023 ( 0 hom., 4 hem., cov: 21)
Exomes đť‘“: 0.000022 ( 0 hom. 6 hem. )
Consequence
DACH2
NM_053281.3 missense
NM_053281.3 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 4.30
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 Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1886057).
BP6
?
Variant X-86812876-C-T is Benign according to our data. Variant chrX-86812876-C-T is described in ClinVar as [Benign]. Clinvar id is 208891.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High Hemizygotes in GnomAd at 4 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DACH2 | NM_053281.3 | c.1261C>T | p.Pro421Ser | missense_variant | 8/12 | ENST00000373125.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DACH2 | ENST00000373125.9 | c.1261C>T | p.Pro421Ser | missense_variant | 8/12 | 1 | NM_053281.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000235 AC: 26AN: 110844Hom.: 0 Cov.: 21 AF XY: 0.000121 AC XY: 4AN XY: 33064
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GnomAD3 exomes AF: 0.0000719 AC: 12AN: 166831Hom.: 0 AF XY: 0.0000743 AC XY: 4AN XY: 53815
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GnomAD4 exome AF: 0.0000221 AC: 24AN: 1084688Hom.: 0 Cov.: 28 AF XY: 0.0000170 AC XY: 6AN XY: 352972
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Abnormality of neuronal migration Benign:1
Benign, no assertion criteria provided | clinical testing | Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire | Oct 31, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.;D
Sift4G
Benign
T;T;T;D;T;D
Polyphen
B;B;.;.;.;.
Vest4
MVP
MPC
0.37
ClinPred
T
GERP RS
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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