rs2273195

Positions:

• chr1-40314169-G-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.249+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,610,956 control chromosomes in the GnomAD database, including 5,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1239 hom., cov: 32)
  • Exomes 𝑓: 0.063 (4202 hom.)
• Consequence: COL9A2 NM_001852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-40314169-G-T is Benign according to our data. Variant chr1-40314169-G-T is described in ClinVar as [Benign]. Clinvar id is 258384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A2	NM_001852.4	c.249+36C>A		intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A2	ENST00000372748.8	c.249+36C>A		intron_variant		1	NM_001852.4	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16136 AN: 152020 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0819

GnomAD3 exomes AF: 0.0879 AC: 22101 AN: 251302 Hom.: 1405 AF XY: 0.0858 AC XY: 11659 AN XY: 135824

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.0923

Gnomad ASJ exome AF: 0.0645

Gnomad EAS exome AF: 0.200

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.0427

Gnomad NFE exome AF: 0.0492

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0625 AC: 91204 AN: 1458818 Hom.: 4202 Cov.: 32 AF XY: 0.0641 AC XY: 46524 AN XY: 725900

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.0905

Gnomad4 ASJ exome AF: 0.0640

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0420

Gnomad4 NFE exome AF: 0.0471

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.106 AC: 16172 AN: 152138 Hom.: 1239 Cov.: 32 AF XY: 0.108 AC XY: 8036 AN XY: 74406

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0800

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0506

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.0632 Hom.: 724

Bravo AF: 0.112

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2273195; hg19: chr1-40779841; COSMIC: COSV65607270; COSMIC: COSV65607270;