NM_000094.4(COL7A1):c.7344G>A (p.Val2448=) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 27, 2023
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:: RCV000414113.8

Allele description

NM_000094.4(COL7A1):c.7344G>A (p.Val2448=)

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.7344G>A (p.Val2448=)

HGVS:

NC_000003.12:g.48570639C>T
NG_007065.1:g.29614G>A
NM_000094.4:c.7344G>AMANE SELECT
NP_000085.1:p.Val2448=
NP_000085.1:p.Val2448=
LRG_286t1:c.7344G>A
LRG_286:g.29614G>A
LRG_286p1:p.Val2448=
NC_000003.11:g.48608072C>T
NM_000094.3:c.7344G>A

Note:

Although this allele was reported to be intronic in the paper by Gardella et al., 1996 (PubMed 8755915), the sequence in Figure 4 was used to confirm that this is now annotated to be at the 3' end of the exon.

Nucleotide change:

IVS95DS, G-A, -1

Links:

OMIM: 120120.0010; dbSNP: rs201728948

NCBI 1000 Genomes Browser:

rs201728948

Molecular consequence:

NM_000094.4:c.7344G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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ribulose-1,5-bisphosphate carboxylase large subunit, partial (chloroplast) [Elwe...
ribulose-1,5-bisphosphate carboxylase large subunit, partial (chloroplast) [Elwendia persica]
gi|2191633468|gb|UKR35593.1|

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PsbA, partial (chloroplast) [Elwendia persica]
PsbA, partial (chloroplast) [Elwendia persica]
gi|183987433|gb|ACC65735.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490507	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 22, 2021)	germline	clinical testing	Citation Link,
SCV000964501	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 27, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17576681, 9536098, 8755915, 10504458, 12485454, 16271705, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490507

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 22, 2021)

germline

clinical testing

Citation Link,

SCV000964501

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 27, 2023)

germline

clinical testing

PubMed (7)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000490507.3

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

Description

Analysis of mRNA derived from a DEB patient showed that c.7344 G>A may produce both normal and abnormal size transcripts; in the abnormal transcript, the last 7 nucleotides of exon 95 are missing due to usage of a cryptic splice donor site located 7bp upstream of the natural donor site (Gardella et al., 1996); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 8755915, 12485454, 29334134, 10504458, 16271705, 31167965, 31001817, 34597860, 33274474)

#	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 Invitae, SCV000964501.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

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 altered splicing and introduces a premature termination codon (PMID: 8755915). The resulting mRNA is expected to undergo nonsense-mediated decay. This sequence change affects codon 2448 of the COL7A1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL7A1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs201728948, gnomAD 0.006%). This variant has been observed in individual(s) with autosomal recessive dystrophic epidermolysis bullosa (PMID: 10504458, 12485454, 16271705). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372349). 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: Sep 16, 2024

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