COL9A1 p.Pro576Pro

Variant names:

• chr6-70253420-C-C
• NM_001851.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr6-70253421--
• chr6-70253421-A-G
• chr6-70253421-A-T
• chr6-70253421-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001851.6(COL9A1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL9A1 NM_001851.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 0 publications found

Genes affected

COL9A1 (HGNC:2217): (collagen type IX alpha 1 chain) This gene encodes one of the three alpha chains of type IX collagen, which is a minor (5-20%) collagen component of hyaline cartilage. Type IX collagen is usually found in tissues containing type II collagen, a fibrillar collagen. Studies in knockout mice have shown that synthesis of the alpha 1 chain is essential for assembly of type IX collagen molecules, a heterotrimeric molecule, and that lack of type IX collagen is associated with early onset osteoarthritis. Mutations in this gene are associated with osteoarthritis in humans, with multiple epiphyseal dysplasia, 6, a form of chondrodysplasia, and with Stickler syndrome, a disease characterized by ophthalmic, orofacial, articular, and auditory defects. Two transcript variants that encode different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

COL9A1 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 6

  Inheritance: AD, Unknown, AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Stickler syndrome, type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp, G2P
• multiple epiphyseal dysplasia due to collagen 9 anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Stickler syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001851.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A1	NM_001851.6	MANE Select	c.		exon_region	Exon 26 of 38	NP_001842.3
	COL9A1	NM_001377289.1		c.		exon_region	Exon 21 of 33	NP_001364218.1	A0A804HIB6
	COL9A1	NM_078485.4		c.		exon_region	Exon 20 of 32	NP_511040.2	P20849-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A1	ENST00000357250.11	TSL:1 MANE Select	c.		exon_region	Exon 26 of 38	ENSP00000349790.6	P20849-1
	COL9A1	ENST00000320755.12	TSL:1	c.		exon_region	Exon 20 of 32	ENSP00000315252.7	P20849-2
	COL9A1	ENST00000683980.2		c.		exon_region	Exon 21 of 33	ENSP00000506990.1	A0A804HIB6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-70963123;