NM_003000.3(SDHB):c.287-3C>G AND multiple conditions

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 8, 2020
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:: RCV001215683.2

Allele description

NM_003000.3(SDHB):c.287-3C>G

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.287-3C>G

HGVS:

NC_000001.11:g.17028739G>C
NG_012340.1:g.30432C>G
NM_003000.3:c.287-3C>GMANE SELECT
LRG_316t1:c.287-3C>G
LRG_316:g.30432C>G
NC_000001.10:g.17355234G>C
NM_003000.2:c.287-3C>G

Links:

dbSNP: rs1553177772

NCBI 1000 Genomes Browser:

rs1553177772

Molecular consequence:

NM_003000.3:c.287-3C>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Gastrointestinal stromal tumor
Synonyms:: Gastrointestinal Stromal Sarcoma; Gastrointestinal stromal tumor, somatic; Gastrointestinal stroma tumor
Identifiers:: MONDO: MONDO:0011719; MeSH: D046152; MedGen: C0238198; Orphanet: 44890; OMIM: 606764; Human Phenotype Ontology: HP:0100723

Name:: Paragangliomas 4 (PGL4)
Synonyms:: CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Pheochromocytoma, extraadrenal and cervical paraganglioma; Paragangliomas, hereditary extraadrenal; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007273; MedGen: C1861848; Orphanet: 29072; OMIM: 115310

Name:: Pheochromocytoma
Synonyms:: Chromaffinoma; Chromaffin paraganglioma; Chromaffin tumor; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008233; MedGen: C0031511; Orphanet: 29072; OMIM: 171300; Human Phenotype Ontology: HP:0002666

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001387440	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 8, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23434467, 30050099, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001387440

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 8, 2020)

germline

clinical testing

PubMed (5)
[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

Citations

PubMed

[Familial paraganglioma syndrome: phenotype and relevance of a new SDHB mutation].

Díaz-Soto G, Serrano Morte A, Rodríguez Martín C, García-Talavera P, Abril CM, Puig-Domingo M.

Med Clin (Barc). 2013 May 13;140(10):453-7. doi: 10.1016/j.medcli.2012.11.030. Epub 2013 Feb 21. Spanish.

PubMed [citation]

PMID:: 23434467

Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma.

Richter S, Gieldon L, Pang Y, Peitzsch M, Huynh T, Leton R, Viana B, Ercolino T, Mangelis A, Rapizzi E, Menschikowski M, Aust D, Kroiss M, Beuschlein F, Gudziol V, Timmers HJ, Lenders J, Mannelli M, Cascon A, Pacak K, Robledo M, Eisenhofer G, et al.

Genet Med. 2019 Mar;21(3):705-717. doi: 10.1038/s41436-018-0106-5. Epub 2018 Jul 27.

PubMed [citation]

PMID:: 30050099
PMCID:: PMC6353556

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001387440.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 3 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with paraganglioma or pheochromocytomas (PMID: 23434467, 30050099). ClinVar contains an entry for this variant (Variation ID: 438419). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Dec 17, 2022

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