rs730880315
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001024630.4(RUNX2):c.1228dup(p.Leu410ProfsTer80) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RUNX2
NM_001024630.4 frameshift
NM_001024630.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
RUNX2 (HGNC:10472): (RUNX family transcription factor 2) This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Two regions of potential trinucleotide repeat expansions are present in the N-terminal region of the encoded protein, and these and other mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-45546964-T-TC is Pathogenic according to our data. Variant chr6-45546964-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 9307.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX2 | NM_001024630.4 | c.1228dup | p.Leu410ProfsTer80 | frameshift_variant | 9/9 | ENST00000647337.2 | |
RUNX2 | NM_001015051.4 | c.1162dup | p.Leu388ProfsTer80 | frameshift_variant | 8/8 | ||
RUNX2 | NM_001278478.2 | c.1120dup | p.Leu374ProfsTer80 | frameshift_variant | 6/6 | ||
RUNX2 | NM_001369405.1 | c.1186dup | p.Leu396ProfsTer80 | frameshift_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX2 | ENST00000647337.2 | c.1228dup | p.Leu410ProfsTer80 | frameshift_variant | 9/9 | NM_001024630.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cleidocranial dysostosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at