NM_000393.5(COL5A2):c.1977G>A (p.Pro659=) AND Ehlers-Danlos syndrome, classic type, 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV002229088.7

Allele description [Variation Report for NM_000393.5(COL5A2):c.1977G>A (p.Pro659=)]

NM_000393.5(COL5A2):c.1977G>A (p.Pro659=)

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.1977G>A (p.Pro659=)

HGVS:

NC_000002.12:g.189062865C>T
NG_011799.3:g.167437G>A
NM_000393.5:c.1977G>AMANE SELECT
NP_000384.2:p.Pro659=
LRG_738t1:c.1977G>A
LRG_738:g.167437G>A
LRG_738p1:p.Pro659=
NC_000002.11:g.189927591C>T
NG_011799.2:g.122015G>A
NM_000393.3:c.1977G>A

Links:

dbSNP: rs863223491

NCBI 1000 Genomes Browser:

rs863223491

Molecular consequence:

NM_000393.5:c.1977G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000631574	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31517854, 17576681, 9536098, 33834621, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000631574

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (5)
[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

A case of Ehlers-Danlos syndrome presenting with widened atrophic scars of forehead, elbow, knee, and pretibial area: A case report.

Xu X, Wang Z, Zan T.

Medicine (Baltimore). 2019 Sep;98(37):e17138. doi: 10.1097/MD.0000000000017138.

PubMed [citation]

PMID:: 31517854
PMCID:: PMC6750314

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000631574.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects codon 659 of the COL5A2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL5A2 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of COL5A2-related Ehlers-Danlos syndrome (PMID: 31517854, 33834621). In at least one individual the variant was observed to be de novo. This variant is also known as c.1997G>A. ClinVar contains an entry for this variant (Variation ID: 213101). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 29, but is expected to preserve the integrity of the reading-frame (PMID: 33834621). For these reasons, this variant has been classified as 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: Jun 17, 2024

ClinVar

Relating variation to medicine