NM_000088.4(COL1A1):c.697-2_697-1del AND Osteogenesis imperfecta type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 20, 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:: RCV001948547.3

Allele description [Variation Report for NM_000088.4(COL1A1):c.697-2_697-1del]

NM_000088.4(COL1A1):c.697-2_697-1del

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:

Deletion

Cytogenetic location:

17q21.33

Genomic location:

Preferred name:

NM_000088.4(COL1A1):c.697-2_697-1del

HGVS:

NC_000017.11:g.50197234_50197235del
NG_007400.1:g.9405_9406del
NM_000088.4:c.697-2_697-1delMANE SELECT
LRG_1:g.9405_9406del
NC_000017.10:g.48274595_48274596del

Links:

dbSNP: rs67163050

NCBI 1000 Genomes Browser:

rs67163050

Molecular consequence:

NM_000088.4:c.697-2_697-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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029B_S24 RNA-seq
029B_S24 RNA-seq

biosample
Acidovorax sp. strain:SUPP1855
Acidovorax sp. strain:SUPP1855
Draft genome sequence of Acidovorax sp. SUPP1855

BioProject
Profile neighbors for GEO Profiles (Select 71226354) (200)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 5766272) (20)
GEO Profiles
Homo sapiens isolate:CHM13
Homo sapiens isolate:CHM13
Homo sapiens isolate:CHM13 RefSeq Genome sequencing and assembly

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002203565	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 20, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17078022, 16199547, 7942841, 9295084, 9443882, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002203565

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 20, 2023)

germline

clinical testing

PubMed (6)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002203565.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Disruption of this splice site has been observed in individuals with osteogenesis imperfecta (PMID: 17078022; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 9 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). ClinVar contains an entry for this variant (Variation ID: 1431197). 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.

#	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: Feb 20, 2024

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