1-40312132-T-C

Variant names:

• chr1-40312132-T-C
• rs78091688
• NM_001852.4:c.364-20A>G

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.364-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,592,960 control chromosomes in the GnomAD database, including 3,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (944 hom., cov: 31)
  • Exomes 𝑓: 0.039 (2249 hom.)
• Consequence: COL9A2 NM_001852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.23

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=-0.84).
• BP6: Variant 1-40312132-T-C is Benign according to our data. Variant chr1-40312132-T-C is described in ClinVar as [Benign]. Clinvar id is 258388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40312132-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4	c.364-20A>G		intron_variant	Intron 7 of 31	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8	c.364-20A>G		intron_variant	Intron 7 of 31	1	NM_001852.4	ENSP00000361834.3

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12638 AN: 151398 Hom.: 932 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0602

GnomAD3 exomes AF: 0.0602 AC: 13309 AN: 221050 Hom.: 750 AF XY: 0.0570 AC XY: 6762 AN XY: 118686

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.0681

Gnomad ASJ exome AF: 0.0191

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.0824

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0442

GnomAD4 exome AF: 0.0387 AC: 55851 AN: 1441470 Hom.: 2249 Cov.: 32 AF XY: 0.0390 AC XY: 27919 AN XY: 715410

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.0669

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.0260

Gnomad4 OTH exome AF: 0.0486

GnomAD4 genome AF: 0.0837 AC: 12676 AN: 151490 Hom.: 944 Cov.: 31 AF XY: 0.0850 AC XY: 6289 AN XY: 73994

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0614

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0577 Hom.: 113

Bravo AF: 0.0910

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.7
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs78091688; hg19: chr1-40777804;