rs72944910

chr1-40304753-G-Achr1-40304753-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001852.4(COL9A2):c.1161+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,526,022 control chromosomes in the GnomAD database, including 5,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1267 hom., cov: 33)
  • Exomes 𝑓: 0.061 (3763 hom.)
• Consequence: COL9A2 NM_001852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.856

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-40304753-G-A is Benign according to our data. Variant chr1-40304753-G-A is described in ClinVar as [Benign]. Clinvar id is 258368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A2	NM_001852.4	c.1161+41C>T		intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A2	ENST00000372748.8	c.1161+41C>T		intron_variant		1	NM_001852.4	P1
COL9A2	ENST00000482722.5	n.1464+41C>T		intron_variant, non_coding_transcript_variant		1
COL9A2	ENST00000466267.1	n.126+41C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16284 AN: 152132 Hom.: 1254 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0783

GnomAD3 exomes AF: 0.0920 AC: 14081 AN: 153012 Hom.: 920 AF XY: 0.0895 AC XY: 7205 AN XY: 80490

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0577

Gnomad EAS exome AF: 0.198

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0523

Gnomad NFE exome AF: 0.0489

Gnomad OTH exome AF: 0.0689

GnomAD4 exome AF: 0.0608 AC: 83502 AN: 1373772 Hom.: 3763 Cov.: 28 AF XY: 0.0618 AC XY: 41921 AN XY: 678156

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0587

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0506

Gnomad4 NFE exome AF: 0.0459

Gnomad4 OTH exome AF: 0.0718

GnomAD4 genome AF: 0.107 AC: 16335 AN: 152250 Hom.: 1267 Cov.: 33 AF XY: 0.109 AC XY: 8130 AN XY: 74448

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0447 Hom.: 47

Bravo AF: 0.114

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.6
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs72944910; hg19: chr1-40770425; COSMIC: COSV65622826; COSMIC: COSV65622826;