NM_000393.5(COL5A2):c.1924-11T>C AND Ehlers-Danlos syndrome, classic type, 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 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:: RCV003595499.3

Allele description [Variation Report for NM_000393.5(COL5A2):c.1924-11T>C]

NM_000393.5(COL5A2):c.1924-11T>C

Gene:

COL5A2:collagen type V alpha 2 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000393.5(COL5A2):c.1924-11T>C

HGVS:

NC_000002.12:g.189062929A>G
NG_011799.3:g.167373T>C
NM_000393.5:c.1924-11T>CMANE SELECT
LRG_738t1:c.1924-11T>C
LRG_738:g.167373T>C
NC_000002.11:g.189927655A>G

Links:

dbSNP: rs2469294833

NCBI 1000 Genomes Browser:

rs2469294833

Molecular consequence:

NM_000393.5:c.1924-11T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Ehlers-Danlos syndrome, classic type, 1 (EDSCL1)
Synonyms:: EHLERS-DANLOS SYNDROME, GRAVIS TYPE; EHLERS-DANLOS SYNDROME, SEVERE CLASSIC TYPE; Ehlers-Danlos syndrome, type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019567; MedGen: C0268335; OMIM: 130000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004343666	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28485813, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004343666

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 10, 2023)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients.

Colombi M, Dordoni C, Venturini M, Ciaccio C, Morlino S, Chiarelli N, Zanca A, Calzavara-Pinton P, Zoppi N, Castori M, Ritelli M.

Clin Genet. 2017 Dec;92(6):624-631. doi: 10.1111/cge.13052. Epub 2017 Sep 4.

PubMed [citation]

PMID:: 28485813

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004343666.2

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 28485813; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 28 of the COL5A2 gene. It does not directly change the encoded amino acid sequence of the COL5A2 protein.

#	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: May 16, 2025

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