rs148008235

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1

The NM_001852.4(COL9A2):​c.2019G>A​(p.Ser673=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,614,084 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

COL9A2
NM_001852.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -1.27
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 1-40301233-C-T is Benign according to our data. Variant chr1-40301233-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196777.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.27 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00152 (232/152280) while in subpopulation AFR AF= 0.00525 (218/41562). AF 95% confidence interval is 0.00467. There are 0 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL9A2NM_001852.4 linkuse as main transcriptc.2019G>A p.Ser673= synonymous_variant 32/32 ENST00000372748.8 NP_001843.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL9A2ENST00000372748.8 linkuse as main transcriptc.2019G>A p.Ser673= synonymous_variant 32/321 NM_001852.4 ENSP00000361834 P1
COL9A2ENST00000482722.5 linkuse as main transcriptn.2322G>A non_coding_transcript_exon_variant 31/311

Frequencies

GnomAD3 genomes
AF:
0.00152
AC:
231
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00524
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
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:
0.0000441
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000440
AC:
110
AN:
250044
Hom.:
0
AF XY:
0.000325
AC XY:
44
AN XY:
135338
show subpopulations
Gnomad AFR exome
AF:
0.00588
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000622
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000186
AC:
272
AN:
1461804
Hom.:
1
Cov.:
31
AF XY:
0.000158
AC XY:
115
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00591
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.00152
AC:
232
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.00142
AC XY:
106
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00525
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000720
Hom.:
0
Bravo
AF:
0.00167
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 02, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 10, 2021- -
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 06, 2015- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Epiphyseal dysplasia, multiple, 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
7.6
DANN
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148008235; hg19: chr1-40766905; API