NM_003000.3(SDHB):c.286+1G>A AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 13, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001541605.15

Allele description [Variation Report for NM_003000.3(SDHB):c.286+1G>A]

NM_003000.3(SDHB):c.286+1G>A

Gene:

SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_003000.3(SDHB):c.286+1G>A

HGVS:

NC_000001.11:g.17033059C>T
NG_012340.1:g.26112G>A
NM_001407361.1:c.286+1G>A
NM_003000.3:c.286+1G>AMANE SELECT
LRG_316t1:c.286+1G>A
LRG_316:g.26112G>A
NC_000001.10:g.17359554C>T
NM_003000.2:c.286+1G>A

Links:

dbSNP: rs786201063

NCBI 1000 Genomes Browser:

rs786201063

Molecular consequence:

NM_001407361.1:c.286+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_003000.3:c.286+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001759624	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 15, 2021)	germline	clinical testing	Citation Link,
SCV002050215	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Pathogenic (May 13, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001759624

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 15, 2021)

germline

clinical testing

Citation Link,

SCV002050215

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Pathogenic
(May 13, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV001759624.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31492822, 17102085, 29623478, 19802898, 19454582, 28152038, 17200167, 25683602, 22517557, 28374168, 26960314, 27539324, 16912137, 17308434, 25525159)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002050215.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The SDHB c.286+1G>A variant (rs786201063), also known as IVS3+1G>A, is reported in the literature in multiple individuals affected with paragangliomas and pheochromocytomas (Brouwers 2006, Isobe 2007, Pandit 2016, Timmers 2007). This variant is reported in ClinVar (Variation ID: 183757). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron three, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. References: Brouwers FM et al. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab. 2006 Nov;91(11):4505-9. PMID: 16912137. Isobe K et al. Novel germline mutations in the SDHB and SDHD genes in Japanese pheochromocytomas. Horm Res. 2007;68(2):68-71. PMID: 17308434. Pandit R et al. Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma. Eur J Endocrinol. 2016 Oct;175(4):311-23. PMID: 27539324. Timmers HJ et al. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab. 2007 Mar;92(3):779-86. PMID: 17200167.

#	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: Apr 20, 2024

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