X-86812915-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_053281.3(DACH2):c.1300C>T(p.Pro434Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,205,549 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P434H) has been classified as Uncertain significance.
Frequency
Consequence
NM_053281.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DACH2 | NM_053281.3 | c.1300C>T | p.Pro434Ser | missense_variant | 8/12 | ENST00000373125.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DACH2 | ENST00000373125.9 | c.1300C>T | p.Pro434Ser | missense_variant | 8/12 | 1 | NM_053281.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000270 AC: 3AN: 111302Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33480
GnomAD3 exomes AF: 0.000121 AC: 22AN: 181308Hom.: 0 AF XY: 0.0000456 AC XY: 3AN XY: 65844
GnomAD4 exome AF: 0.0000219 AC: 24AN: 1094247Hom.: 0 Cov.: 28 AF XY: 0.00000834 AC XY: 3AN XY: 359725
GnomAD4 genome ? AF: 0.0000270 AC: 3AN: 111302Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33480
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2023 | The c.1300C>T (p.P434S) 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 1300, causing the proline (P) at amino acid position 434 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at