NM_000088.4(COL1A1):c.1056+1G>A AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 31, 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:: RCV003050487.3

Allele description [Variation Report for NM_000088.4(COL1A1):c.1056+1G>A]

NM_000088.4(COL1A1):c.1056+1G>A

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.1056+1G>A

HGVS:

NC_000017.11:g.50195922C>T
NG_007400.1:g.10718G>A
NM_000088.4:c.1056+1G>AMANE SELECT
LRG_1:g.10718G>A
NC_000017.10:g.48273283C>T

Molecular consequence:

NM_000088.4:c.1056+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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003442407	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 31, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17078022, 30886339, 16199547, 7942841, 9295084, 9443882, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442407

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 31, 2022)

germline

clinical testing

PubMed (7)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans.

Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Körkkö J, Prockop DJ, De Paepe A, Coucke P, Symoens S, Glorieux FH, Roughley PJ, Lund AM, Kuurila-Svahn K, Hartikka H, Cohn DH, Krakow D, Mottes M, Schwarze U, Chen D, et al.

Hum Mutat. 2007 Mar;28(3):209-21. Review.

PubMed [citation]

PMID:: 17078022
PMCID:: PMC4144349

Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients.

Maioli M, Gnoli M, Boarini M, Tremosini M, Zambrano A, Pedrini E, Mordenti M, Corsini S, D'Eufemia P, Versacci P, Celli M, Sangiorgi L.

Eur J Hum Genet. 2019 Jul;27(7):1090-1100. doi: 10.1038/s41431-019-0373-x. Epub 2019 Mar 18.

PubMed [citation]

PMID:: 30886339
PMCID:: PMC6777444

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442407.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

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. This variant is also known as IVS16 +1G>A. Disruption of this splice site has been observed in individual(s) with osteogenesis imperfecta (PMID: 17078022, 30886339). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 16 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).

#	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

Last Updated: Sep 29, 2024

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