rs1555164872

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_001844.5(COL2A1):​c.3489+163_3597+2del variant causes a exon loss, splice acceptor, splice donor, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

COL2A1
NM_001844.5 exon_loss, splice_acceptor, splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.32
Variant links:
Genes affected
COL2A1 (HGNC:2200): (collagen type II alpha 1 chain) This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.024193548 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-47975960-TACAGCAGGGCCGGTTTCGCCTGATCGTCCACGGGGACCAGGAGGCCCAATGGGGCCAGGGATTCCATTAGCACCATCTTTGCCAGAGGGACCGACGGGGCCAGGAGGACCCTGCAAGAGAGAGAGGTCGTGAGGAAAGAGTGGTCACCACAGGGAAGGCTGGGGAGTCGCTGGGGCTGGGTAGGTGGCTGTCCTGATAGCACCAGCCACTCCGCCCCCAGTTCTTCACATGCTCAGTCATGGAACCCTAAGTTGGTCTCTATTTGGCCAAGAACCAGCAGGATAGCTCCATGGCTTGCCTACCCTCCTAAGCTCCTCTTTGTAAAATGCTGTTCTGTCTGACAGCGAGAGGCTGATTCATGTTTGTCTTACAGCCATTGTGGCCTCAGGCG-T is Pathogenic according to our data. Variant chr12-47975960-TACAGCAGGGCCGGTTTCGCCTGATCGTCCACGGGGACCAGGAGGCCCAATGGGGCCAGGGATTCCATTAGCACCATCTTTGCCAGAGGGACCGACGGGGCCAGGAGGACCCTGCAAGAGAGAGAGGTCGTGAGGAAAGAGTGGTCACCACAGGGAAGGCTGGGGAGTCGCTGGGGCTGGGTAGGTGGCTGTCCTGATAGCACCAGCCACTCCGCCCCCAGTTCTTCACATGCTCAGTCATGGAACCCTAAGTTGGTCTCTATTTGGCCAAGAACCAGCAGGATAGCTCCATGGCTTGCCTACCCTCCTAAGCTCCTCTTTGTAAAATGCTGTTCTGTCTGACAGCGAGAGGCTGATTCATGTTTGTCTTACAGCCATTGTGGCCTCAGGCG-T is described in ClinVar as [Pathogenic]. Clinvar id is 17351.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-47975960-TACAGCAGGGCCGGTTTCGCCTGATCGTCCACGGGGACCAGGAGGCCCAATGGGGCCAGGGATTCCATTAGCACCATCTTTGCCAGAGGGACCGACGGGGCCAGGAGGACCCTGCAAGAGAGAGAGGTCGTGAGGAAAGAGTGGTCACCACAGGGAAGGCTGGGGAGTCGCTGGGGCTGGGTAGGTGGCTGTCCTGATAGCACCAGCCACTCCGCCCCCAGTTCTTCACATGCTCAGTCATGGAACCCTAAGTTGGTCTCTATTTGGCCAAGAACCAGCAGGATAGCTCCATGGCTTGCCTACCCTCCTAAGCTCCTCTTTGTAAAATGCTGTTCTGTCTGACAGCGAGAGGCTGATTCATGTTTGTCTTACAGCCATTGTGGCCTCAGGCG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL2A1NM_001844.5 linkc.3489+163_3597+2del exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant Exon 50 of 54 ENST00000380518.8 NP_001835.3 P02458-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL2A1ENST00000380518.8 linkc.3489+163_3597+2del exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant Exon 50 of 54 1 NM_001844.5 ENSP00000369889.3 P02458-2
COL2A1ENST00000337299.7 linkc.3282+163_3390+2del exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant Exon 49 of 53 1 ENSP00000338213.6 P02458-1
COL2A1ENST00000546974.1 linkn.342+163_450+2del splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant Exon 5 of 6 1
COL2A1ENST00000493991.5 linkn.2575+163_2683+2del splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant Exon 33 of 37 2

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia congenita Pathogenic:1
May 26, 1989
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555164872; hg19: chr12-48369743; API