NM_003002.4(SDHD):c.170-1G>T AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jun 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000641037.2

Allele description [Variation Report for NM_003002.4(SDHD):c.170-1G>T]

NM_003002.4(SDHD):c.170-1G>T

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.170-1G>T
HGVS:
  • NC_000011.10:g.112088866G>T
  • NG_012337.3:g.7020G>T
  • NG_033145.1:g.2933C>A
  • NM_001276503.2:c.169+893G>T
  • NM_001276504.2:c.53-1G>T
  • NM_001276506.2:c.170-1G>T
  • NM_003002.4:c.170-1G>TMANE SELECT
  • LRG_9t1:c.170-1G>T
  • LRG_9:g.7020G>T
  • NC_000011.9:g.111959590G>T
  • NM_003002.3:c.170-1G>T
Links:
dbSNP: rs1306475361
NCBI 1000 Genomes Browser:
rs1306475361
Molecular consequence:
  • NM_001276503.2:c.169+893G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001276504.2:c.53-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001276506.2:c.170-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_003002.4:c.170-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Carney-Stratakis syndrome
Synonyms:
Paraganglioma and gastric stromal sarcoma; Paraganglioma and gastrointestinal stromal tumor; Paraganglioma and GIST; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011740; MedGen: C1847319; Orphanet: 97286; OMIM: 606864
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
Name:
Paragangliomas 1 (PGL1)
Synonyms:
PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; PGL 1; Paragangliomas familial 1; See all synonyms [MedGen]
Identifiers:
MedGen: C1868633; Orphanet: 29072; OMIM: 168000
Name:
Cowden syndrome 3 (CWS3)
Identifiers:
MONDO: MONDO:0014045; MedGen: CN166604; Orphanet: 201

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000762655Invitaecriteria provided, single submitter
Pathogenic
(Jun 12, 2018)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma.

Dannenberg H, Dinjens WN, Abbou M, Van Urk H, Pauw BK, Mouwen D, Mooi WJ, de Krijger RR.

Clin Cancer Res. 2002 Jul;8(7):2061-6.

PubMed [citation]
PMID:
12114404

The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas.

Burnichon N, Rohmer V, Amar L, Herman P, Leboulleux S, Darrouzet V, Niccoli P, Gaillard D, Chabrier G, Chabolle F, Coupier I, Thieblot P, Lecomte P, Bertherat J, Wion-Barbot N, Murat A, Venisse A, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP; PGL.NET network..

J Clin Endocrinol Metab. 2009 Aug;94(8):2817-27. doi: 10.1210/jc.2008-2504. Epub 2009 May 19.

PubMed [citation]
PMID:
19454582
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000762655.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 2 of the SDHD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with paraganglioma in several families (PMID: 18551016, 12509798), and has been observed in several individuals affected with SDHD-related disease (PMID: 12114404, 19075037, 22566194, 29545045). ClinVar contains an entry for this variant (Variation ID: 438434). Experimental studies have shown that this variant causes abnormal splicing which creates a transcript that lacks exon 3, resulting in a downstream truncation (PMID: 12509798). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Dec 2, 2021

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