NM_004628.5(XPC):c.1872+2T>C AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 13, 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:: RCV001780086.4

Allele description [Variation Report for NM_004628.5(XPC):c.1872+2T>C]

NM_004628.5(XPC):c.1872+2T>C

Gene:

XPC:XPC complex subunit, DNA damage recognition and repair factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_004628.5(XPC):c.1872+2T>C

Other names:

NM_004628.5:c.1872+2T>C

HGVS:

NC_000003.12:g.14158009A>G
NG_011763.1:g.25664T>C
NM_001354726.2:c.1293+2T>C
NM_001354727.2:c.1872+2T>C
NM_001354729.2:c.1854+2T>C
NM_001354730.2:c.1626+248T>C
NM_004628.5:c.1872+2T>CMANE SELECT
LRG_472:g.25664T>C
NC_000003.11:g.14199509A>G

Links:

dbSNP: rs2125024504

NCBI 1000 Genomes Browser:

rs2125024504

Molecular consequence:

NM_001354730.2:c.1626+248T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354726.2:c.1293+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354727.2:c.1872+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354729.2:c.1854+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004628.5:c.1872+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002016353	MutSpliceDB: a database of splice sites variants effects on splicing, NIH	no classification provided	not provided	somatic	research	Citation Link,
SCV003295766	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 23173980, 25256075, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002016353

MutSpliceDB: a database of splice sites variants effects on splicing, NIH

no classification provided

not provided

somatic

research

Citation Link,

SCV003295766

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 13, 2022)

germline

clinical testing

PubMed (4)
[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
not provided	somatic	not applicable	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Molecular genetic analysis of 16 XP-C patients from Germany: environmental factors predominately contribute to phenotype variations.

Schäfer A, Hofmann L, Gratchev A, Laspe P, Schubert S, Schürer A, Ohlenbusch A, Tzvetkov M, Hallermann C, Reichrath J, Schön MP, Emmert S.

Exp Dermatol. 2013 Jan;22(1):24-9. doi: 10.1111/exd.12052. Epub 2012 Nov 22.

PubMed [citation]

PMID:: 23173980

See all PubMed Citations (4)

Details of each submission

From MutSpliceDB: a database of splice sites variants effects on splicing, NIH, SCV002016353.1

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

Description

Intron inclusion between exons 9 & 10, based on review of RNA-seq in TCGA-BF-AAP4-01A tumor which has XPC NM_004628.5:c.1872+2T>C variant

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003295766.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

ClinVar contains an entry for this variant (Variation ID: 1322012). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals affected with XPC-related conditions. This sequence change affects a donor splice site in intron 9 of the XPC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is not present in population databases (gnomAD no frequency).

#	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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