NM_000090.4(COL3A1):c.81del (p.Val28fs) AND Ehlers-Danlos syndrome, type 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 7, 2020
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:: RCV000474877.6

Allele description [Variation Report for NM_000090.4(COL3A1):c.81del (p.Val28fs)]

NM_000090.4(COL3A1):c.81del (p.Val28fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_000090.4(COL3A1):c.81del (p.Val28fs)

HGVS:

NC_000002.12:g.188984761del
NG_007404.1:g.15389del
NM_000090.4:c.81delMANE SELECT
NP_000081.2:p.Val28fs
LRG_3:g.15389del
NC_000002.11:g.189849487del
NC_000002.11:g.189849487delT
NM_000090.3:c.81delT

Protein change:

V28fs

Links:

dbSNP: rs1060500200

NCBI 1000 Genomes Browser:

rs1060500200

Molecular consequence:

NM_000090.4:c.81del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000541806	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 7, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24922459, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541806

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 7, 2020)

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

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

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, SCV000541806.5

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

Description

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). This sequence change deletes 1 nucleotide from exon 2 of the COL3A1 mRNA (c.81delT), causing a frameshift at codon 28. This creates a premature translational stop signal (p.Val28Leufs*38) and is expected to result in an absent or disrupted protein product.

#	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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