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NM_000088.4(COL1A1):c.858+1G>A AND Osteogenesis imperfecta type I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 16, 2022
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:
RCV003041318.2

Allele description

NM_000088.4(COL1A1):c.858+1G>A

Genes:
LOC126862586:CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:48273702-48274901 [Gene]
COL1A1:collagen type I alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.33
Genomic location:
Preferred name:
NM_000088.4(COL1A1):c.858+1G>A
HGVS:
  • NC_000017.11:g.50196616C>T
  • NG_007400.1:g.10024G>A
  • NG_087083.1:g.376C>T
  • NM_000088.4:c.858+1G>AMANE SELECT
  • LRG_1:g.10024G>A
  • NC_000017.10:g.48273977C>T
Molecular consequence:
  • NM_000088.4:c.858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Osteogenesis imperfecta type I (OI1)
Synonyms:
OI, TYPE I; Osteogenesis imperfecta type 1; OI type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008146; MedGen: C0023931; Orphanet: 666; OMIM: 166200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003442449Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 16, 2022) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta.

Li L, Mao B, Li S, Xiao J, Wang H, Zhang J, Ren X, Wang Y, Wu Y, Cao Y, Lu C, Gao J, You Y, Zhao F, Geng X, Xiao Y, Jiang C, Ye Y, Yang T, Zhao X, Zhang X.

Hum Mutat. 2019 May;40(5):588-600. doi: 10.1002/humu.23718. Epub 2019 Feb 25.

PubMed [citation]
PMID:
30715774

COL1A1/2 Pathogenic Variants and Phenotype Characteristics in Ukrainian Osteogenesis Imperfecta Patients.

Zhytnik L, Maasalu K, Pashenko A, Khmyzov S, Reimann E, Prans E, Kõks S, Märtson A.

Front Genet. 2019;10:722. doi: 10.3389/fgene.2019.00722.

PubMed [citation]
PMID:
31447884
PMCID:
PMC6696896
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV003442449.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

Disruption of this splice site has been observed in individual(s) with osteogenesis imperfecta (PMID: 9443882, 30715774, 31447884). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Studies have shown that disruption of this splice site alters COL1A1 gene expression (PMID: 9443882). This variant is also known as IVS12+1G>A. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 12 of the COL1A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024