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NM_021975.4(RELA):c.1034-2A>C AND Mucocutaneous ulceration

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 1, 2018
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:
RCV000853280.1

Allele description [Variation Report for NM_021975.4(RELA):c.1034-2A>C]

NM_021975.4(RELA):c.1034-2A>C

Gene:
RELA:RELA proto-oncogene, NF-kB subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.1
Genomic location:
Preferred name:
NM_021975.4(RELA):c.1034-2A>C
HGVS:
  • NC_000011.10:g.65655002T>G
  • NG_029971.1:g.12971A>C
  • NM_001145138.2:c.1025-2A>C
  • NM_001243984.2:c.1034-209A>C
  • NM_001243985.2:c.1034-2A>C
  • NM_001404657.1:c.1067-2A>C
  • NM_001404658.1:c.1007-2A>C
  • NM_001404659.1:c.821-2A>C
  • NM_001404660.1:c.716-2A>C
  • NM_001404661.1:c.653-2A>C
  • NM_001404662.1:c.941-2A>C
  • NM_001404663.1:c.941-2A>C
  • NM_021975.4:c.1034-2A>CMANE SELECT
  • NC_000011.9:g.65422473T>G
  • NM_021975.3:c.1034-2A>C
Links:
dbSNP: rs1590931704
NCBI 1000 Genomes Browser:
rs1590931704
Molecular consequence:
  • NM_001243984.2:c.1034-209A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001145138.2:c.1025-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001243985.2:c.1034-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404657.1:c.1067-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404658.1:c.1007-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404659.1:c.821-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404660.1:c.716-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404661.1:c.653-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404662.1:c.941-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001404663.1:c.941-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_021975.4:c.1034-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

Name:
Mucocutaneous ulceration
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000996112Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 1, 2018) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996112.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This variant affects the canonical splice acceptor site of intron 10 and is therefore predicted to alter splicing and exert a loss-of-function effect. A different canonical splice donor site variant in RELA has been reported in an individual with recurrent mucocutaneous ulcers, fever, and elevated inflammatory markers (PMID: 28600438). Family members of the described patient were genotyped and the RELA variant was found to segregate with disease in an autosomal dominant fashion (PMID: 28600438). A separate publication has reported a de novo nonsense variant in a patient with lymphoproliferative disease and autoimmune cytopenias (PMID: 29305315), indicating that the phenotype associated with loss-of-function mutations in RELA may be variable. The c.1034-2A>C variant is absent from the gnomAD population database and is thus presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, this variant is classified as a likely pathogenic change.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Jun 10, 2023