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NM_003002.4(SDHD):c.266_267dup (p.Ala90fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 18, 2024
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:
RCV002428739.3

Allele description [Variation Report for NM_003002.4(SDHD):c.266_267dup (p.Ala90fs)]

NM_003002.4(SDHD):c.266_267dup (p.Ala90fs)

Gene:
SDHD:succinate dehydrogenase complex subunit D [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_003002.4(SDHD):c.266_267dup (p.Ala90fs)
HGVS:
  • NC_000011.10:g.112088961CT[3]
  • NG_012337.3:g.7115CT[3]
  • NG_033145.1:g.2835AG[3]
  • NM_001276503.2:c.169+988CT[3]
  • NM_001276504.2:c.149_150dup
  • NM_001276506.2:c.266_267dup
  • NM_003002.4:c.266_267dupMANE SELECT
  • NP_001263433.1:p.Ala51fs
  • NP_001263435.1:p.Ala90fs
  • NP_002993.1:p.Ala90fs
  • LRG_9t1:c.266_267dup
  • LRG_9:g.7115CT[3]
  • LRG_9p1:p.Ala90fs
  • NC_000011.9:g.111959685CT[3]
  • NM_003002.2:c.266_267dupCT
  • NR_077060.2:n.299CT[3]
Protein change:
A51fs
Molecular consequence:
  • NM_001276504.2:c.149_150dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276506.2:c.266_267dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003002.4:c.266_267dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001276503.2:c.169+988CT[3] - intron variant - [Sequence Ontology: SO:0001627]
  • NR_077060.2:n.299CT[3] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002743485Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 18, 2024) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002743485.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.266_267dupCT pathogenic mutation, located in coding exon 3 of the SDHD gene, results from a duplication of CT at nucleotide position 266, causing a translational frameshift with a predicted alternate stop codon (p.A90Lfs*46). This alteration occurs at the 3' terminus of theSDHD gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 43% of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). In addition, this variant has been observed in at least one individual with a personal and/or family history that is consistent with SDHD-related paraganglioma-pheochromocytoma syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Aug 11, 2024