NM_001271893.4:c.223G>A
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001271893.4(TWIST2):c.223G>A(p.Glu75Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001271893.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TWIST2 | NM_001271893.4 | c.223G>A | p.Glu75Lys | missense_variant | Exon 1 of 2 | ENST00000612363.2 | NP_001258822.1 | |
TWIST2 | NM_057179.3 | c.223G>A | p.Glu75Lys | missense_variant | Exon 1 of 2 | NP_476527.1 | ||
TWIST2 | XR_007069137.1 | n.354G>A | non_coding_transcript_exon_variant | Exon 1 of 2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TWIST2 | ENST00000612363.2 | c.223G>A | p.Glu75Lys | missense_variant | Exon 1 of 2 | 1 | NM_001271893.4 | ENSP00000482581.1 | ||
TWIST2 | ENST00000448943.2 | c.223G>A | p.Glu75Lys | missense_variant | Exon 1 of 2 | 1 | ENSP00000405176.2 | |||
TWIST2 | ENST00000710607.1 | c.223G>A | p.Glu75Lys | missense_variant | Exon 1 of 2 | ENSP00000518373.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.17e-7 AC: 1AN: 1395318Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 689052
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Ablepharon macrostomia syndrome Pathogenic:2
A heterozygous missense p.Glu75Lys was reported to be associated with Ablepharon macrostomia syndrome in 7 families (Marchegiani et al. 2015). This variant was not found in ExAC database and our in-house Thai exome database (consisted of 1084 Thai exome controls). We classified this as pathogenic variant by ACMG Guidelines, 2015 based on >/=2 strong criteria [PS1, PS2, and PS3 (Functional study by Marchegiani et al. 2015)]. -
- -
Inborn genetic diseases Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at