rs864309724
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP3_ModeratePP5
The NM_004991.4(MECOM):c.2812C>T(p.Arg938Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R938Q) has been classified as Pathogenic.
Frequency
Consequence
NM_004991.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECOM | NM_004991.4 | c.2812C>T | p.Arg938Trp | missense_variant | 12/17 | ENST00000651503.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECOM | ENST00000651503.2 | c.2812C>T | p.Arg938Trp | missense_variant | 12/17 | NM_004991.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456170Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 724312
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 Pathogenic:2Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 18, 2020 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 03, 2015 | - - |
Uncertain significance, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Dec 03, 2018 | The heterozygous p.Arg815Trp variant in MECOM was identified by our study in one individual with radioulnar synostosis with amegakaryocytic thrombocytopenia. This variant was absent from large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg815Trp variant is uncertain. ACMG/AMP Criteria applied: PM2 (Richards 2015). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 27, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29519864, 20091385, 26581901, 29540340, 29097497, 29200407, 32098966, Pronama2021[Review], 35219593, 35470277, 36515795) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at