rs372138746
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001024630.4(RUNX2):c.254C>A(p.Ala85Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RUNX2
NM_001024630.4 missense
NM_001024630.4 missense
Scores
1
5
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.79
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19505489).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RUNX2 | NM_001024630.4 | c.254C>A | p.Ala85Glu | missense_variant | Exon 3 of 9 | ENST00000647337.2 | NP_001019801.3 | |
| RUNX2 | NM_001369405.1 | c.212C>A | p.Ala71Glu | missense_variant | Exon 1 of 7 | NP_001356334.1 | ||
| RUNX2 | NM_001015051.4 | c.254C>A | p.Ala85Glu | missense_variant | Exon 3 of 8 | NP_001015051.3 | ||
| RUNX2 | NM_001278478.2 | c.212C>A | p.Ala71Glu | missense_variant | Exon 1 of 6 | NP_001265407.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1342798Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 664560
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1342798
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
664560
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;D;D;D;.;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;.;D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;.;N;N;.;N;.
REVEL
Benign
Sift
Benign
.;T;.;T;T;.;T;.
Sift4G
Benign
T;T;.;T;T;T;T;T
Polyphen
0.0, 0.081
.;B;B;B;.;.;B;.
Vest4
MVP
MPC
0.79
ClinPred
D
GERP RS
Varity_R
gMVP
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