rs149666891
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM2PP2BP4_StrongBP6_Very_StrongBS1
The NM_001378457.1(DMXL2):c.3880G>A(p.Ala1294Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,613,928 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1294G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378457.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMXL2 | NM_001378457.1 | c.3880G>A | p.Ala1294Thr | missense_variant | 18/44 | ENST00000560891.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMXL2 | ENST00000560891.6 | c.3880G>A | p.Ala1294Thr | missense_variant | 18/44 | 1 | NM_001378457.1 | A1 | |
DMXL2 | ENST00000543779.6 | c.3880G>A | p.Ala1294Thr | missense_variant | 18/43 | 1 | P4 | ||
DMXL2 | ENST00000251076.9 | c.3880G>A | p.Ala1294Thr | missense_variant | 18/43 | 1 | A1 | ||
DMXL2 | ENST00000449909.7 | c.2765-4210G>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00158 AC: 241AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000367 AC: 92AN: 250756Hom.: 0 AF XY: 0.000310 AC XY: 42AN XY: 135606
GnomAD4 exome AF: 0.000127 AC: 186AN: 1461630Hom.: 1 Cov.: 32 AF XY: 0.000105 AC XY: 76AN XY: 727106
GnomAD4 genome ? AF: 0.00158 AC: 240AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124AN XY: 74470
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Dec 18, 2017 | BS1, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, and is predicted to be tolerated by multiple functional prediction tools. - |
DMXL2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at