rs11498192

chr6-45422749-AGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGC-Achr6-45422749-AGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGC-AGGCGGCGGCGGCGGCTGCchr6-45422749-AGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGC-AGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGCGGCGGCGGCGGCGGCTGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

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
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001024630.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX2	NM_001024630.4	c.225_260del	p.Ala78_Ala89del	inframe_deletion	3/9	ENST00000647337.2
RUNX2	NM_001015051.4	c.225_260del	p.Ala78_Ala89del	inframe_deletion	3/8
RUNX2	NM_001278478.2	c.183_218del	p.Ala64_Ala75del	inframe_deletion	1/6
RUNX2	NM_001369405.1	c.183_218del	p.Ala64_Ala75del	inframe_deletion	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX2	ENST00000647337.2	c.225_260del	p.Ala78_Ala89del	inframe_deletion	3/9		NM_001024630.4	P4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.0000246 AC: 4 AN: 162630 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 92448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000115

Gnomad SAS exome AF: 0.0000910

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1379934 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 685076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000615

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11498192; hg19: chr6-45390486;