rs3831927

chr1-40302811-TGGAGGGAGGGAG-Tchr1-40302811-TGGAGGGAGGGAG-TGGAGchr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGchr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAGchr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAGGGAGchr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAGGGAGGGAG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001852.4(COL9A2):c.1604-14_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 0.0000831 in 553,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000079 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: COL9A2 NM_001852.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-40302811-TGGAGGGAGGGAG-T is Benign according to our data. Variant chr1-40302811-TGGAGGGAGGGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2820807.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A2	NM_001852.4	c.1604-14_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.1604-14_1604-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001852.4	P1
COL9A2	ENST00000482722.5	n.1907-14_1907-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
COL9A2	ENST00000427563.1	n.360-14_360-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3
COL9A2	ENST00000466267.1	n.569-14_569-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000795 AC: 1 AN: 125862 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000105 AC: 45 AN: 428014 Hom.: 0 AF XY: 0.0000736 AC XY: 17 AN XY: 231000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000164

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000166

Gnomad4 OTH exome AF: 0.000154

GnomAD4 genome AF: 0.00000795 AC: 1 AN: 125862 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 59778

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000168

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2023

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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;