rs12038020

Positions:

• chr1-40302604-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001852.4(COL9A2):​c.1792+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,590,078 control chromosomes in the GnomAD database, including 1,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (294 hom., cov: 32)
  • Exomes 𝑓: 0.012 (733 hom.)
• Consequence: COL9A2 NM_001852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.438

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-40302604-C-T is Benign according to our data. Variant chr1-40302604-C-T is described in ClinVar as [Benign]. Clinvar id is 258377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40302604-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A2	NM_001852.4	c.1792+17G>A		intron_variant		ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8	c.1792+17G>A		intron_variant		1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5	n.2095+17G>A		intron_variant		1
COL9A2	ENST00000466267.1	n.757+17G>A		intron_variant		5
COL9A2	ENST00000427563.1	n.*17G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6225 AN: 152070 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0304 AC: 6505 AN: 214164 Hom.: 249 AF XY: 0.0264 AC XY: 3074 AN XY: 116266

Gnomad AFR exome AF: 0.0999

Gnomad AMR exome AF: 0.0652

Gnomad ASJ exome AF: 0.00106

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.0319

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00176

Gnomad OTH exome AF: 0.0190

GnomAD4 exome AF: 0.0117 AC: 16875 AN: 1437894 Hom.: 733 Cov.: 34 AF XY: 0.0118 AC XY: 8398 AN XY: 713898

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0617

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0317

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.000933

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.0410 AC: 6236 AN: 152184 Hom.: 294 Cov.: 32 AF XY: 0.0410 AC XY: 3053 AN XY: 74408

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0397

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0196 Hom.: 21

Bravo AF: 0.0479

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2016	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. -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12038020; hg19: chr1-40768276;