NM_017841.4(SDHAF2):c.260+2T>C AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 13, 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:: RCV001379058.4

Allele description [Variation Report for NM_017841.4(SDHAF2):c.260+2T>C]

NM_017841.4(SDHAF2):c.260+2T>C

Gene:

SDHAF2:succinate dehydrogenase complex assembly factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.2

Genomic location:

Preferred name:

NM_017841.4(SDHAF2):c.260+2T>C

HGVS:

NC_000011.10:g.61437850T>C
NG_023393.1:g.12726T>C
NM_017841.4:c.260+2T>CMANE SELECT
LRG_519:g.12726T>C
NC_000011.9:g.61205322T>C

Links:

dbSNP: rs2134892557

NCBI 1000 Genomes Browser:

rs2134892557

Molecular consequence:

NM_017841.4:c.260+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary pheochromocytoma-paraganglioma
Synonyms:: Hereditary Paraganglioma-Pheochromocytoma Syndromes; Hereditary Paragangliomas and Pheochromocytomas
Identifiers:: MONDO: MONDO:0017366; MedGen: C1708353

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576782	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 13, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 22241717, 26096992, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576782

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 13, 2020)

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

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

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]

PMID:: 22241717

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001576782.4

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

Description

This variant has not been reported in the literature in individuals with SDHAF2-related conditions. 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. 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). 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. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor 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.

#	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: Feb 28, 2024

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