chr6-45431963-T-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_001024630.4(RUNX2):c.524T>G(p.Met175Arg) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M175V) has been classified as Likely benign.
Frequency
Consequence
NM_001024630.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX2 | NM_001024630.4 | c.524T>G | p.Met175Arg | missense_variant | 4/9 | ENST00000647337.2 | |
RUNX2 | NM_001369405.1 | c.482T>G | p.Met161Arg | missense_variant | 2/7 | ||
RUNX2 | NM_001015051.4 | c.524T>G | p.Met175Arg | missense_variant | 4/8 | ||
RUNX2 | NM_001278478.2 | c.482T>G | p.Met161Arg | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX2 | ENST00000647337.2 | c.524T>G | p.Met175Arg | missense_variant | 4/9 | NM_001024630.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cleidocranial dysostosis Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1997 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jun 20, 2022 | ACMG classification criteria: PS4 moderated, PM2 moderated, PM6 moderated, PP3 supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at