NM_000094.4(COL7A1):c.6145G>A (p.Gly2049Arg) AND Recessive dystrophic epidermolysis bullosa

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2022
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:: RCV002052060.1

Allele description [Variation Report for NM_000094.4(COL7A1):c.6145G>A (p.Gly2049Arg)]

NM_000094.4(COL7A1):c.6145G>A (p.Gly2049Arg)

Gene:

COL7A1:collagen type VII alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000094.4(COL7A1):c.6145G>A (p.Gly2049Arg)

HGVS:

NC_000003.12:g.48575374C>T
NG_007065.1:g.24879G>A
NM_000094.4:c.6145G>AMANE SELECT
NP_000085.1:p.Gly2049Arg
LRG_286:g.24879G>A
NC_000003.11:g.48612807C>T

Protein change:

G2049R

Links:

dbSNP: rs1189071165

NCBI 1000 Genomes Browser:

rs1189071165

Molecular consequence:

NM_000094.4:c.6145G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Recessive dystrophic epidermolysis bullosa (RDEB)
Synonyms:: EPIDERMOLYSIS BULLOSA DYSTROPHICA, AUTOSOMAL RECESSIVE; DYSTROPHIC EPIDERMOLYSIS BULLOSA, AUTOSOMAL RECESSIVE; EPIDERMOLYSIS BULLOSA DYSTROPHICA, HALLOPEAU-SIEMENS TYPE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009179; MedGen: C0079474; Orphanet: 79408; Orphanet: 79409; OMIM: 226600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318471	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9326325, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002318471

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 22, 2022)

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation.

Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers CA, Prost C, Fraitag S, Christiano AM, Uitto J, Lathrop M, Barrandon Y, de Prost Y.

Am J Hum Genet. 1997 Sep;61(3):599-610.

PubMed [citation]

PMID:: 9326325
PMCID:: PMC1715975

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002318471.1

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

Description

A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001047980, PMID:9326325). It is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.962>=0.6, 3CNET: 0.992>=0.75). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 29, 2024

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