rs1555164872

Positions:

• chr12-47975960-TACAGCAGGGCCGGTTTCGCCTGATCGTCCACGGGGACCAGGAGGCCCAATGGGGCCAGGGATTCCATTAGCACCATCTTTGCCAGAGGGACCGACGGGGCCAGGAGGACCCTGCAAGAGAGAGAGGTCGTGAGGAAAGAGTGGTCACCACAGGGAAGGCTGGGGAGTCGCTGGGGCTGGGTAGGTGGCTGTCCTGATAGCACCAGCCACTCCGCCCCCAGTTCTTCACATGCTCAGTCATGGAACCCTAAGTTGGTCTCTATTTGGCCAAGAACCAGCAGGATAGCTCCATGGCTTGCCTACCCTCCTAAGCTCCTCTTTGTAAAATGCTGTTCTGTCTGACAGCGAGAGGCTGATTCATGTTTGTCTTACAGCCATTGTGGCCTCAGGCG-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.32

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]

COL2A1 (HGNC:):

ACMG classification

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 0.023969535 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/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.3489+163_3597+2del		exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant	50/54	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.3489+163_3597+2del		exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant	50/54	1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.3282+163_3390+2del		exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant	49/53	1		ENSP00000338213.6
COL2A1	ENST00000546974.1	n.342+163_450+2del		splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant	5/6	1
COL2A1	ENST00000493991.5	n.2575+163_2683+2del		splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant	33/37	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

Submissions by phenotype

Spondyloepiphyseal dysplasia congenita Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 26, 1989

- -

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: rs1555164872; hg19: chr12-48369743;