1-40302811-TGGAGGGAG-T

Variant names:

• chr1-40302811-TGGAGGGAG-T
• rs3831927
• NM_001852.4:c.1604-10_1604-3delCTCCCTCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001852.4(COL9A2):​c.1604-10_1604-3delCTCCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 551,572 control chromosomes in the GnomAD database, including 1,273 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (512 hom., cov: 30)
  • Exomes 𝑓: 0.017 (761 hom.)
• Consequence: COL9A2 NM_001852.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.54
• Publications: 1 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: Labcorp Genetics (formerly Invitae), 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-40302811-TGGAGGGAG-T is Benign according to our data. Variant chr1-40302811-TGGAGGGAG-T is described in ClinVar as Benign. ClinVar VariationId is 196621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001852.4. 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
	COL9A2	NM_001852.4	MANE Select	c.1604-10_1604-3delCTCCCTCC		splice_region intron	N/A	NP_001843.1	Q14055

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A2	ENST00000372748.8	TSL:1 MANE Select	c.1604-10_1604-3delCTCCCTCC		splice_region intron	N/A	ENSP00000361834.3	Q14055
	COL9A2	ENST00000482722.5	TSL:1	n.1907-10_1907-3delCTCCCTCC		splice_region intron	N/A
	COL9A2	ENST00000869268.1		c.1688-10_1688-3delCTCCCTCC		splice_region intron	N/A	ENSP00000539327.1

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 6743 AN: 125844 Hom.: 507 Cov.: 30

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00800

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000569

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.000168

Gnomad MID AF: 0.0139

Gnomad NFE AF: 0.000688

Gnomad OTH AF: 0.0286

GnomAD2 exomes AF: 0.0106 AC: 1461 AN: 137322 AF XY: 0.00844

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.00855

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000199

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000669

Gnomad OTH exome AF: 0.00606

GnomAD4 exome AF: 0.0174 AC: 7397 AN: 425630 Hom.: 761 AF XY: 0.0139 AC XY: 3192 AN XY: 229902

African (AFR) AF: 0.316 AC: 5475 AN: 17328

American (AMR) AF: 0.0116 AC: 330 AN: 28398

Ashkenazi Jewish (ASJ) AF: 0.000240 AC: 3 AN: 12510

East Asian (EAS) AF: 0.000548 AC: 7 AN: 12776

South Asian (SAS) AF: 0.00125 AC: 76 AN: 60842

European-Finnish (FIN) AF: 0.000146 AC: 4 AN: 27372

Middle Eastern (MID) AF: 0.0192 AC: 47 AN: 2446

European-Non Finnish (NFE) AF: 0.00292 AC: 715 AN: 244578

Other (OTH) AF: 0.0382 AC: 740 AN: 19380

GnomAD4 genome AF: 0.0538 AC: 6778 AN: 125942 Hom.: 512 Cov.: 30 AF XY: 0.0546 AC XY: 3270 AN XY: 59836

African (AFR) AF: 0.183 AC: 6425 AN: 35162

American (AMR) AF: 0.0192 AC: 238 AN: 12388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3148

East Asian (EAS) AF: 0.000569 AC: 2 AN: 3514

South Asian (SAS) AF: 0.00117 AC: 4 AN: 3424

European-Finnish (FIN) AF: 0.000168 AC: 1 AN: 5964

Middle Eastern (MID) AF: 0.0149 AC: 4 AN: 268

European-Non Finnish (NFE) AF: 0.000688 AC: 41 AN: 59562

Other (OTH) AF: 0.0323 AC: 57 AN: 1762

Alfa AF: 0.00164 Hom.: 6

Bravo AF: 0.0518

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=89/11	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3831927; hg19: chr1-40768483;