rs137853213

Positions:

• chr1-40307477-TG-CA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PS1_Moderate PM2 BP6_Very_Strong

The NM_001852.4(COL9A2):​c.976_977delCAinsTG​(p.Gln326Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q326R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL9A2 NM_001852.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: 2.07

Genes affected

COL9A2 (HGNC:2218): (collagen type IX alpha 2 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. This chain is unusual in that, unlike the other two type IX alpha chains, it contains a covalently attached glycosaminoglycan side chain. Mutations in this gene are associated with multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

COL9A2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PS1: Transcript NM_001852.4 (COL9A2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-40307477-TG-CA is Benign according to our data. Variant chr1-40307477-TG-CA is described in ClinVar as [Benign]. Clinvar id is 17145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A2	NM_001852.4	c.976_977delCAinsTG	p.Gln326Trp	missense_variant		ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8	c.976_977delCAinsTG	p.Gln326Trp	missense_variant		1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5	n.1279_1280delCAinsTG		non_coding_transcript_exon_variant	18/31	1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Intervertebral disc disease, susceptibility to Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jul 16, 1999

- -

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: rs137853213; hg19: chr1-40773149;