NM_000090.4(COL3A1):c.80-1G>C AND Ehlers-Danlos syndrome, type 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 10, 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:: RCV000697120.5

Allele description [Variation Report for NM_000090.4(COL3A1):c.80-1G>C]

NM_000090.4(COL3A1):c.80-1G>C

Gene:

COL3A1:collagen type III alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000090.4(COL3A1):c.80-1G>C

HGVS:

NC_000002.12:g.188984759G>C
NG_007404.1:g.15387G>C
NM_000090.4:c.80-1G>CMANE SELECT
LRG_3t1:c.80-1G>C
LRG_3:g.15387G>C
NC_000002.11:g.189849485G>C
NM_000090.3:c.80-1G>C

Links:

dbSNP: rs1559052551

NCBI 1000 Genomes Browser:

rs1559052551

Molecular consequence:

NM_000090.4:c.80-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Ehlers-Danlos syndrome, type 4
Synonyms:: Ehlers-Danlos syndrome vascular type; Ehlers Danlos syndrome, ecchymotic type; Ehlers Danlos syndrome, arterial type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0017314; MedGen: C0268338; Orphanet: 286; OMIM: 130050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000825714	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 24922459, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000825714

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 10, 2023)

germline

clinical testing

PubMed (3)
[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

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

Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).

Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH.

Genet Med. 2014 Dec;16(12):881-8. doi: 10.1038/gim.2014.72. Epub 2014 Jun 12.

PubMed [citation]

PMID:: 24922459

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000825714.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 1 of the COL3A1 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 COL3A1 are known to be pathogenic (PMID: 24922459). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Ehlers-Danlos syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 575032). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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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