NM_000094.4(COL7A1):c.6022C>T (p.Arg2008Cys) AND Recessive dystrophic epidermolysis bullosa

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jun 6, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000789046.7

Allele description [Variation Report for NM_000094.4(COL7A1):c.6022C>T (p.Arg2008Cys)]

NM_000094.4(COL7A1):c.6022C>T (p.Arg2008Cys)

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.6022C>T (p.Arg2008Cys)

HGVS:

NC_000003.12:g.48575497G>A
NG_007065.1:g.24756C>T
NM_000094.4:c.6022C>TMANE SELECT
NP_000085.1:p.Arg2008Cys
NP_000085.1:p.Arg2008Cys
LRG_286t1:c.6022C>T
LRG_286:g.24756C>T
LRG_286p1:p.Arg2008Cys
NC_000003.11:g.48612930G>A
NM_000094.3:c.6022C>T
p.Arg2008Cys

Protein change:

R2008C

Links:

dbSNP: rs1055680335

NCBI 1000 Genomes Browser:

rs1055680335

Molecular consequence:

NM_000094.4:c.6022C>T - 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
SCV000928395	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 9, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002499318	Center for Research in Genodermatoses and Epidermolysis Bullosa, University of Buenos Aires	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25741868, 9740253, 35979658
SCV003807900	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 6, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004035049	Narges Medical Genetic and Prenatal Diagnosis Lab	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV004100630	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	2	not provided	1	not provided	clinical testing

Citations

PubMed

Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa.

Kon A, Pulkkinen L, Ishida-Yamamoto A, Hashimoto I, Uitto J.

J Invest Dermatol. 1998 Sep;111(3):534-7.

PubMed [citation]

PMID:: 9740253

Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype-phenotype correlation.

Natale MI, Manzur GB, Lusso SB, Cella E, Giovo ME, Andrada R, Goitia J, Fernández MF, Della Giovanna PS, Guillamondegui MJ, Domínguez M, Gutiérrez O, Izquierdo A, Hernández Herrera H, Velázquez Perdomo LG, Mistchenko AS, Valinotto LE.

Am J Med Genet A. 2022 Nov;188(11):3153-3161. doi: 10.1002/ajmg.a.62957. Epub 2022 Aug 18.

PubMed [citation]

PMID:: 35979658

See all PubMed Citations (3)

Details of each submission

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV000928395.1

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

Description

PM1, PM2, PM5, PP2, PP3, PP5

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

From Center for Research in Genodermatoses and Epidermolysis Bullosa, University of Buenos Aires, SCV002499318.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	2	not provided

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV003807900.1

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

Description

ACMG classification criteria: PS4 supporting, PM2 moderated, PM3 strong

#	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

From Narges Medical Genetic and Prenatal Diagnosis Lab, SCV004035049.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	not provided

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100630.1

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

Description

The missense variant p.R2008C in COL7A1 (NM_000094.4) has been reported previously in affected indviduals (Escámez MJ et al,2018). It has been submitted to ClinVar as Pathogenic. Other variants affecting this residue have been reported previously. The p.R2008C variant is observed in 1/1,09,206 (0.0009%) alleles from individuals of European (Non-Finnish) background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes.The p.R2008C missense variant is predicted to be damaging by both SIFT and PolyPhen2. The nucleotide c.6022 in COL7A1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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