chr12-47999661-C-A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001844.5(COL2A1):c.292+258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_001844.5 intron
Scores
Clinical Significance
Conservation
Publications
- achondrogenesis type IIInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- Kniest dysplasiaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
- platyspondylic dysplasia, Torrance typeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- spondyloepimetaphyseal dysplasia, Strudwick typeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- spondyloepiphyseal dysplasia congenitaInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- spondyloepiphyseal dysplasia with metatarsal shorteningInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- spondylometaphyseal dysplasiaInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- spondyloperipheral dysplasiaInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Stickler syndrome type 1Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Illumina, Orphanet, Genomics England PanelApp
- Stickler syndrome, type I, nonsyndromic ocularInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- avascular necrosis of femoral head, primary, 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Legg-Calve-Perthes diseaseInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritisInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- otospondylomegaepiphyseal dysplasia, autosomal recessiveInheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
- spondyloepiphyseal dysplasia, Stanescu typeInheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- autosomal dominant rhegmatogenous retinal detachmentInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- dysspondyloenchondromatosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial avascular necrosis of femoral headInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hypochondrogenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- multiple epiphyseal dysplasia, Beighton typeInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- spondylometaphyseal dysplasia, Schmidt typeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- otospondylomegaepiphyseal dysplasiaInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
- vitreoretinopathy with phalangeal epiphyseal dysplasiaInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.292+258G>T | intron_variant | Intron 2 of 53 | 1 | NM_001844.5 | ENSP00000369889.3 | |||
COL2A1 | ENST00000337299.7 | c.86-1230G>T | intron_variant | Intron 1 of 52 | 1 | ENSP00000338213.6 | ||||
COL2A1 | ENST00000474996.6 | n.530+258G>T | intron_variant | Intron 3 of 7 | 3 | |||||
COL2A1 | ENST00000490609.2 | n.*36G>T | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 115110Hom.: 0 Cov.: 17
GnomAD4 exome AF: 0.000494 AC: 19AN: 38448Hom.: 0 Cov.: 0 AF XY: 0.000507 AC XY: 10AN XY: 19706 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
Age Distribution
GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 115138Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0AN XY: 54734
ClinVar
Submissions by phenotype
not provided Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at