NM_001844.5(COL2A1):c.4337del (p.Gly1446fs) AND Stickler syndrome, type I, nonsyndromic ocular

Germline classification:: Uncertain significance (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003338384.2

Allele description [Variation Report for NM_001844.5(COL2A1):c.4337del (p.Gly1446fs)]

NM_001844.5(COL2A1):c.4337del (p.Gly1446fs)

Gene:

COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q13.11

Genomic location:

Preferred name:

NM_001844.5(COL2A1):c.4337del (p.Gly1446fs)

HGVS:

NC_000012.12:g.47973537del
NG_008072.1:g.35969del
NM_001844.5:c.4337delMANE SELECT
NM_033150.3:c.4130del
NP_001835.3:p.Gly1446fs
NP_149162.2:p.Gly1377fs
NC_000012.11:g.48367320del
NM_001844.4:c.4337delG

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

G1377fs

Links:

OMIM: 120140.0041; dbSNP: rs1565664375

NCBI 1000 Genomes Browser:

rs1565664375

Molecular consequence:

NM_001844.5:c.4337del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033150.3:c.4130del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Stickler syndrome, type I, nonsyndromic ocular
Synonyms:: STICKLER SYNDROME, TYPE I, PREDOMINANTLY OCULAR; STICKLER SYNDROME, ATYPICAL
Identifiers:: MONDO: MONDO:0012287; MedGen: C1836080; OMIM: 609508

Recent activity

Clear Turn Off Turn On

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
SCV004048075	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004048075

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004048075.1

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

Description

The frameshift deletion p.G1446Afs*25 in COL2A1 (NM_001844.5) has been reported to ClinVar as Pathogenic. The p.G1446Afs*25 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The frame shifted sequence continues 25 residues until a stop codon is reached. The p.G1446Afs*25 variant is a loss of function variant in the gene COL2A1, which is intolerant of Loss of Function variants. Since, the variant is present in last exon, functional studies will be required to prove protein truncation. For these reasons, this variant has been classified as Uncertain Significance.

#	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: Apr 6, 2024

ClinVar

Relating variation to medicine