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NM_004168.4(SDHA):c.554dup (p.Ala186fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 28, 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:
RCV002350731.2

Allele description [Variation Report for NM_004168.4(SDHA):c.554dup (p.Ala186fs)]

NM_004168.4(SDHA):c.554dup (p.Ala186fs)

Gene:
SDHA:succinate dehydrogenase complex flavoprotein subunit A [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
5p15.33
Genomic location:
Preferred name:
NM_004168.4(SDHA):c.554dup (p.Ala186fs)
HGVS:
  • NC_000005.10:g.225980dup
  • NG_012339.1:g.12740dup
  • NM_001294332.2:c.410dup
  • NM_001330758.2:c.554dup
  • NM_004168.4:c.554dupMANE SELECT
  • NP_001281261.1:p.Ala138fs
  • NP_001317687.1:p.Ala186fs
  • NP_004159.2:p.Ala186fs
  • LRG_315t1:c.554dup
  • LRG_315:g.12740dup
  • LRG_315p1:p.Ala186fs
  • NC_000005.9:g.226094_226095insA
  • NC_000005.9:g.226095dup
  • NM_004168.2:c.554dupA
Protein change:
A138fs
Links:
dbSNP: rs1173940446
NCBI 1000 Genomes Browser:
rs1173940446
Molecular consequence:
  • NM_001294332.2:c.410dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330758.2:c.554dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004168.4:c.554dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002649952Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 28, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches.

Gieldon L, William D, Hackmann K, Jahn W, Jahn A, Wagner J, Rump A, Bechmann N, Nölting S, Knösel T, Gudziol V, Constantinescu G, Masjkur J, Beuschlein F, Timmers HJ, Canu L, Pacak K, Robledo M, Aust D, Schröck E, Eisenhofer G, Richter S, et al.

Cancers (Basel). 2019 Jun 11;11(6). doi:pii: E809. 10.3390/cancers11060809.

PubMed [citation]
PMID:
31212687
PMCID:
PMC6627084

Details of each submission

From Ambry Genetics, SCV002649952.2

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

Description

The c.554dupA variant, located in coding exon 5 of the SDHA gene, results from a duplication of A at nucleotide position 554, causing a translational frameshift with a predicted alternate stop codon (p.A186Gfs*9). This alteration was identified in an individual with a personal history of a head/neck paraganglioma diagnosed under age 30 (Gieldon L et al. Cancers (Basel), 2019 Jun;11:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as "c.553_554insA (p.Ala186fs)" in published literature. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024