NM_000089.4(COL1A2):c.1648G>A (p.Gly550Ser) AND Osteogenesis imperfecta with normal sclerae, dominant form

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 23, 2023
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:: RCV003152809.1

Allele description [Variation Report for NM_000089.4(COL1A2):c.1648G>A (p.Gly550Ser)]

NM_000089.4(COL1A2):c.1648G>A (p.Gly550Ser)

Gene:

COL1A2:collagen type I alpha 2 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.3

Genomic location:

Preferred name:

NM_000089.4(COL1A2):c.1648G>A (p.Gly550Ser)

HGVS:

NC_000007.14:g.94413930G>A
NG_007405.1:g.24370G>A
NM_000089.4:c.1648G>AMANE SELECT
NP_000080.2:p.Gly550Ser
NP_000080.2:p.Gly550Ser
LRG_2t1:c.1648G>A
LRG_2:g.24370G>A
LRG_2p1:p.Gly550Ser
NC_000007.13:g.94043242G>A
NM_000089.3:c.1648G>A

Protein change:

G550S

Molecular consequence:

NM_000089.4:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Osteogenesis imperfecta with normal sclerae, dominant form (OI4)
Synonyms:: Osteogenesis imperfecta type 4; OI type 4; Osteogenesis imperfecta with normal sclerae; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008148; MedGen: C0268363; Orphanet: 666; OMIM: 166220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003841610	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21488275, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841610

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Novel human pathological mutations. Gene symbol: COL1A2. Disease: osteogenesis imperfecta IV.

Lin HY, Chuang CK, Lin SP.

Hum Genet. 2010 Apr;127(4):466. No abstract available.

PubMed [citation]

PMID:: 21488275

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 3billion, SCV003841610.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 0.92). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL1A2-related disorder (PMID: 21488275). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024

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