rs7771980
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001024630.4(RUNX2):c.59-1041T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 152,242 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.082 ( 720 hom., cov: 32)
Exomes 𝑓: 0.13 ( 0 hom. )
Consequence
RUNX2
NM_001024630.4 intron
NM_001024630.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0610
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 6-45421552-T-C is Benign according to our data. Variant chr6-45421552-T-C is described in ClinVar as [Benign]. Clinvar id is 1164339.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX2 | NM_001024630.4 | c.59-1041T>C | intron_variant | ENST00000647337.2 | |||
LOC124901324 | XR_007059602.1 | n.480A>G | non_coding_transcript_exon_variant | 2/2 | |||
RUNX2 | NM_001015051.4 | c.59-1041T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX2 | ENST00000647337.2 | c.59-1041T>C | intron_variant | NM_001024630.4 | P4 | ||||
ENST00000606796.1 | n.454A>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0817 AC: 12426AN: 152108Hom.: 723 Cov.: 32
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GnomAD4 exome AF: 0.125 AC: 2AN: 16Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2AN XY: 12
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GnomAD4 genome ? AF: 0.0816 AC: 12424AN: 152226Hom.: 720 Cov.: 32 AF XY: 0.0874 AC XY: 6506AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at