NM_001852.4(COL9A2):c.1242del (p.Gly415fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 10, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001873178.13

Allele description [Variation Report for NM_001852.4(COL9A2):c.1242del (p.Gly415fs)]

NM_001852.4(COL9A2):c.1242del (p.Gly415fs)

Gene:

COL9A2:collagen type IX alpha 2 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_001852.4(COL9A2):c.1242del (p.Gly415fs)

HGVS:

NC_000001.11:g.40304371del
NG_008031.1:g.17903del
NM_001852.3:c.1242del
NM_001852.4:c.1242delMANE SELECT
NP_001843.1:p.Gly415fs
NC_000001.10:g.40770037del
NC_000001.10:g.40770043del
NM_001852.3:c.1242delC

Protein change:

G415fs

Links:

dbSNP: rs756694568

NCBI 1000 Genomes Browser:

rs756694568

Molecular consequence:

NM_001852.4:c.1242del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

ADGRB3-DT ADGRB3 divergent transcript [Homo sapiens]
ADGRB3-DT ADGRB3 divergent transcript [Homo sapiens]
Gene ID:101928307

Gene
Gene Links for GEO Profiles (Select 97677720) (1)
Gene
Gene Links for GEO Profiles (Select 27154082) (1)
Gene
UNC119B unc-119 lipid binding chaperone B [Homo sapiens]
UNC119B unc-119 lipid binding chaperone B [Homo sapiens]
Gene ID:84747

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002208316	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21671392, 33356723, 28492532
SCV002821022	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2022)	germline	clinical testing	Citation Link,
SCV003842596	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 8, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002208316

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002821022

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Nov 1, 2022)

germline

clinical testing

Citation Link,

SCV003842596

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Mar 8, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome.

Baker S, Booth C, Fillman C, Shapiro M, Blair MP, Hyland JC, Ala-Kokko L.

Am J Med Genet A. 2011 Jul;155A(7):1668-72. doi: 10.1002/ajmg.a.34071. Epub 2011 Jun 10.

PubMed [citation]

PMID:: 21671392

Autosomal recessive Stickler syndrome associated with homozygous mutations in the COL9A2 gene.

Kjellström U, Martell S, Brobeck C, Andréasson S.

Ophthalmic Genet. 2021 Apr;42(2):161-169. doi: 10.1080/13816810.2020.1861309. Epub 2020 Dec 27.

PubMed [citation]

PMID:: 33356723

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002208316.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gly415Glufs*116) in the COL9A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL9A2 are known to be pathogenic (PMID: 21671392, 33356723). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COL9A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 632106). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV002821022.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

COL9A2: PVS1, PM2, PM3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneDx, SCV003842596.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine