chr6-45422749-AGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGC-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP3BS2
The NM_001024630.4(RUNX2):c.225_260del(p.Ala78_Ala89del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000362 in 1,379,934 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000036 ( 1 hom. )
Consequence
RUNX2
NM_001024630.4 inframe_deletion
NM_001024630.4 inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.35
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_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001024630.4
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RUNX2 | NM_001024630.4 | c.225_260del | p.Ala78_Ala89del | inframe_deletion | 3/9 | ENST00000647337.2 | NP_001019801.3 | |
| RUNX2 | NM_001015051.4 | c.225_260del | p.Ala78_Ala89del | inframe_deletion | 3/8 | NP_001015051.3 | ||
| RUNX2 | NM_001278478.2 | c.183_218del | p.Ala64_Ala75del | inframe_deletion | 1/6 | NP_001265407.1 | ||
| RUNX2 | NM_001369405.1 | c.183_218del | p.Ala64_Ala75del | inframe_deletion | 1/7 | NP_001356334.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RUNX2 | ENST00000647337.2 | c.225_260del | p.Ala78_Ala89del | inframe_deletion | 3/9 | NM_001024630.4 | ENSP00000495497 | P4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
29
GnomAD3 exomes AF: 0.0000246 AC: 4AN: 162630Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 92448
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GnomAD4 exome AF: 0.00000362 AC: 5AN: 1379934Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 685076
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GnomAD4 genome
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29
ClinVar
Not reported inComputational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at