NM_017841.2(SDHAF2):c.261-2A>T AND Hereditary Paraganglioma-Pheochromocytoma Syndromes

Clinical significance:Likely pathogenic (Last evaluated: Jan 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_017841.2(SDHAF2):c.261-2A>T]


SDHAF2:succinate dehydrogenase complex assembly factor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000011.10:g.61438002A>T
  • NG_023393.1:g.12878A>T
  • NM_017841.2:c.261-2A>T
  • LRG_519t1:c.261-2A>T
  • LRG_519:g.12878A>T
  • NC_000011.9:g.61205474A>T
dbSNP: rs745989557
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_017841.2:c.261-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]


Hereditary Paraganglioma-Pheochromocytoma Syndromes (PGL-PCC)
Hereditary Paragangliomas and Pheochromocytomas
MONDO: MONDO:0017366; MedGen: C1708353

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000958808Invitaecriteria provided, single submitter
Likely pathogenic
(Jan 5, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Germline mutations and genotype-phenotype associations in head and neck paraganglioma patients with negative family history in China.

Zhu WD, Wang ZY, Chai YC, Wang XW, Chen DY, Wu H.

Eur J Med Genet. 2015 Sep;58(9):433-8. doi: 10.1016/j.ejmg.2015.05.008. Epub 2015 Jun 19.

PubMed [citation]

Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients.

Piccini V, Rapizzi E, Bacca A, Di Trapani G, Pulli R, Giachè V, Zampetti B, Lucci-Cordisco E, Canu L, Corsini E, Faggiano A, Deiana L, Carrara D, Tantardini V, Mariotti S, Ambrosio MR, Zatelli MC, Parenti G, Colao A, Pratesi C, Bernini G, Ercolino T, et al.

Endocr Relat Cancer. 2012 Apr 10;19(2):149-55. doi: 10.1530/ERC-11-0369. Print 2012 Apr.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000958808.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change affects an acceptor splice site in intron 2 of the SDHAF2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SDHAF2-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHAF2 are known to be pathogenic (PMID: 22241717, 26096992). 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 27, 2020

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