1-40302811-TGGAGGGAGGGAG-TGGAG

Position:

• chr1-40302811-TGGAGGGAGGGAG-TGGAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001852.4(COL9A2):​c.1604-10_1604-3del variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.54

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 -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 id is 196621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40302811-TGGAGGGAG-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A2	NM_001852.4	c.1604-10_1604-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A2	ENST00000372748.8	c.1604-10_1604-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001852.4	P1
COL9A2	ENST00000482722.5	n.1907-10_1907-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
COL9A2	ENST00000427563.1	n.360-10_360-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3
COL9A2	ENST00000466267.1	n.569-10_569-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.0106 AC: 1461 AN: 137322 Hom.: 112 AF XY: 0.00844 AC XY: 628 AN XY: 74414

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 SAS exome AF: 0.00103

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

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.000240

Gnomad4 EAS exome AF: 0.000548

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.000146

Gnomad4 NFE exome AF: 0.00292

Gnomad4 OTH exome AF: 0.0382

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000569

Gnomad4 SAS AF: 0.00117

Gnomad4 FIN AF: 0.000168

Gnomad4 NFE AF: 0.000688

Gnomad4 OTH AF: 0.0323

Bravo AF: 0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2018	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2015	- -

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: rs3831927; hg19: chr1-40768483;