rs3831927

Variant names:

• chr1-40302811-TGGAGGGAGGGAG-T
• rs3831927
• NM_001852.4:c.1604-14_1604-3delCTCCCTCCCTCC

Your query was ambiguous. Multiple possible variants found:

• chr1-40302811-TGGAGGGAGGGAG-T
• chr1-40302811-TGGAGGGAGGGAG-TGGAG
• chr1-40302811-TGGAGGGAGGGAG-TGGAGGGAG
• chr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAG
• chr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAGGGAG
• chr1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAGGGAGGGAG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001852.4(COL9A2):​c.1604-14_1604-3delCTCCCTCCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 553,876 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• 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 VariationId is 2820807.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4	c.1604-14_1604-3delCTCCCTCCCTCC		splice_region_variant, intron_variant	Intron 29 of 31	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8	c.1604-14_1604-3delCTCCCTCCCTCC		splice_region_variant, intron_variant	Intron 29 of 31	1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5	n.1907-14_1907-3delCTCCCTCCCTCC		splice_region_variant, intron_variant	Intron 28 of 30	1
COL9A2	ENST00000427563.1	n.360-14_360-3delCTCCCTCCCTCC		splice_region_variant, intron_variant	Intron 6 of 6	3
COL9A2	ENST00000466267.1	n.569-14_569-3delCTCCCTCCCTCC		splice_region_variant, intron_variant	Intron 9 of 10	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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17364

American (AMR) AF: 0.00 AC: 0 AN: 28414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12520

East Asian (EAS) AF: 0.00 AC: 0 AN: 12810

South Asian (SAS) AF: 0.0000164 AC: 1 AN: 60888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2454

European-Non Finnish (NFE) AF: 0.000166 AC: 41 AN: 246662

Other (OTH) AF: 0.000154 AC: 3 AN: 19500

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 35094

American (AMR) AF: 0.00 AC: 0 AN: 12368

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 3428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59558

Other (OTH) AF: 0.00 AC: 0 AN: 1748

Alfa AF: 0.00 Hom.: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=81/19	polymorphism

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;