rs209916

Variant names:

• chr1-40310087-G-A
• rs209916
• NM_001852.4:c.792+24C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-40310087-G-A
• chr1-40310087-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001852.4(COL9A2):​c.792+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00893 in 1,613,922 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (113 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (118 hom.)
• Consequence: COL9A2 NM_001852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0390
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Stickler syndrome, type 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-40310087-G-A is Benign according to our data. Variant chr1-40310087-G-A is described in ClinVar as Benign. ClinVar VariationId is 258396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4	c.792+24C>T		intron_variant	Intron 15 of 31	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8	c.792+24C>T		intron_variant	Intron 15 of 31	1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5	n.1095+24C>T		intron_variant	Intron 14 of 30	1
COL9A2	ENST00000417105.6	c.*203C>T		downstream_gene_variant		5		ENSP00000388493.2
COL9A2	ENST00000488463.6	n.*24C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3691 AN: 152150 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.0114 AC: 2860 AN: 251284 AF XY: 0.0102

Gnomad AFR exome AF: 0.0649

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.000652

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.00688

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.00732 AC: 10692 AN: 1461654 Hom.: 118 Cov.: 34 AF XY: 0.00719 AC XY: 5230 AN XY: 727110

African (AFR) AF: 0.0645 AC: 2159 AN: 33478

American (AMR) AF: 0.00718 AC: 321 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00677 AC: 177 AN: 26132

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.00495 AC: 427 AN: 86258

European-Finnish (FIN) AF: 0.0222 AC: 1184 AN: 53402

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5766

European-Non Finnish (NFE) AF: 0.00502 AC: 5586 AN: 1111818

Other (OTH) AF: 0.0124 AC: 746 AN: 60376

GnomAD4 genome AF: 0.0244 AC: 3715 AN: 152268 Hom.: 113 Cov.: 32 AF XY: 0.0242 AC XY: 1801 AN XY: 74462

African (AFR) AF: 0.0668 AC: 2775 AN: 41540

American (AMR) AF: 0.0105 AC: 160 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4824

European-Finnish (FIN) AF: 0.0245 AC: 260 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00606 AC: 412 AN: 68012

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0253

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.50
DANN	Benign	0.64
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs209916; hg19: chr1-40775759;