VCV003024130.1 - ClinVar

NM_001709.5(BDNF):c.[*1785G>T;-21-14109C>G196G>A]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely risk allele

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_001709.5(BDNF):c.[*1785G>T;-21-14109C>G196G>A]

Other names: -
Functional consequence: -
Links: -

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BDNF		-	-	GRCh38 GRCh37	17	150
BDNF-AS		-	-	GRCh38 GRCh37	-	135

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Post-traumatic stress disorder	Likely risk allele (1)	no assertion criteria provided	Dec 11, 2023	RCV003881714.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely risk allele (Dec 11, 2023)	no assertion criteria provided Method: clinical testing	Post-traumatic stress disorder (Codominant) Affected status: no, yes Allele origin: inherited	Thompson Institute, University of the Sunshine Coast Accession: SCV004244433.1 First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024	Publications: PubMed (2) PubMed: 21167606‚ 17293537 pmc: 3237476 pmc: 3237476 Comment: It was observed that 61.1% of all PTSD participants possess all three of the variants rs2049045 (p=0.0134, OR=6.26, CI=1.61 - 30.3), rs6265 (p=0.0279, OR=4.72, CI=1.28 … (more) It was observed that 61.1% of all PTSD participants possess all three of the variants rs2049045 (p=0.0134, OR=6.26, CI=1.61 - 30.3), rs6265 (p=0.0279, OR=4.72, CI=1.28 - 20.86) and rs11030099 (p=0.0294, OR=5.11, CI=1.25 - 24.55) compared to only 17.6% of non-PTSD participants. Additionally, 92% of these PTSD participants were heterozygous for all three variants, apart from one participant who was homozygous for two of the three variants. We also identified a significant decrease in proBDNF levels (by up to 82%) between those who had all 3SNP variants and those who had <3SNP variants (two-tailed p = 0.023), which suggests that this haplotype may contribute to PTSD susceptibility following trauma exposure. (less) Observation 1: Number of individuals with the variant: 17 Clinical Features: Posttraumatic stress symptom (present) Age: 43-77 years Sex: mixed Ethnicity/Population group: Caucasion Geographic origin: Australia Comment on evidence: We observed that 61.1% of all PTSD participants exhibited all three SNPs rs2049045 (p=0.0134, OR=6.26, CI=1.61 - 30.3), rs6265 (p=0.0279, OR=4.72, CI=1.28 - 20.86), and … (more) We observed that 61.1% of all PTSD participants exhibited all three SNPs rs2049045 (p=0.0134, OR=6.26, CI=1.61 - 30.3), rs6265 (p=0.0279, OR=4.72, CI=1.28 - 20.86), and rs11030099 (p=0.0294, OR=5.11, CI=1.25 - 24.55) and a significant reduction in pro-BDNF (p=0.023) when compared to participants carrying <3SNPs. Analysis through linkage disequilibrium across the Caucasian population uncovered a strong pairwise D value across all three SNP’s (D>0.97) (less) Method: Genomic DNA from whole blood was extracted utilising DNeasy Blood and Tissue Kit (Qiagen Australia) according to the manufacturer’s protocols. Purified DNA was quantified and measured for tolerances by Nanodrop (Thermo Fisher) and stored at -20°C. Forward and reverse primers for each BDNF region were designed through Primer3 and synthesised by Sigma Aldrich. Regions of interest were amplified via polymerase chain reaction (PCR) utilising Platinum Superfi Master mix (Thermo Fisher) with the manufacturer’s recommended amplification conditions and quality checked via agarose gel electrophoresis. PCR products were analysed via Sanger Sequencing by Macrogen (Korea). Testing laboratory: Macrogen Korea Date variant was reported to submitter: 2023-09-05 Testing laboratory interpretation: not provided Observation 2: Number of individuals with the variant: 5 Clinical Features: Posttraumatic stress symptom (absent) Age: 50-76 years Sex: mixed Ethnicity/Population group: Caucasion Geographic origin: Australia Comment on evidence: We observed that 17% (3/14) of non-PTSD participants carried the 3SNP variant. Method: Genomic DNA from whole blood was extracted utilising DNeasy Blood and Tissue Kit (Qiagen Australia) according to the manufacturer’s protocols. Purified DNA was quantified and measured for tolerances by Nanodrop (Thermo Fisher) and stored at -20°C. Forward and reverse primers for each BDNF region were designed through Primer3 and synthesised by Sigma Aldrich. Regions of interest were amplified via polymerase chain reaction (PCR) utilising Platinum Superfi Master mix (Thermo Fisher) with the manufacturer’s recommended amplification conditions and quality checked via agarose gel electrophoresis. PCR products were analysed via Sanger Sequencing by Macrogen (Korea). Testing laboratory: Macrogen (Korea) Date variant was reported to submitter: 2023-09-05 Testing laboratory interpretation: not provided

Comment:

It was observed that 61.1% of all PTSD participants possess all three of the variants rs2049045 (p=0.0134, OR=6.26, CI=1.61 - 30.3), rs6265 (p=0.0279, OR=4.72, CI=1.28 - 20.86) and rs11030099 (p=0.0294, OR=5.11, CI=1.25 - 24.55) compared to only 17.6% of non-PTSD participants. Additionally, 92% of these PTSD participants were heterozygous for all three variants, apart from one participant who was homozygous for two of the three variants. We also identified a significant decrease in proBDNF levels (by up to 82%) between those who had all 3SNP variants and those who had <3SNP variants (two-tailed p = 0.023), which suggests that this haplotype may contribute to PTSD susceptibility following trauma exposure.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Brain derived neurotrophic factor (BDNF) expression is regulated by microRNAs miR-26a and miR-26b allele-specific binding.	Caputo V	PloS one	2011	PMC3237476
The role of BDNF genetic polymorphisms in bipolar disorder with psychiatric comorbidities.	Neves FS	Journal of affective disorders	2011	PMID: 21167606
A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.	Soliman F	Science (New York, N.Y.)	2010	PMID: 20075215
Genetic variants in brain-derived neurotrophic factor associated with Alzheimer's disease.	Huang R	Journal of medical genetics	2007	PMID: 17293537
The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study.	Rosa A	American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics	2006	PMID: 16389585
Illness-specific association of val66met BDNF polymorphism with performance on Wisconsin Card Sorting Test in bipolar mood disorder.	Rybakowski JK	Molecular psychiatry	2006	PMID: 16222333
BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.	Karamohamed S	Neurology	2005	PMID: 16344533
The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis.	Zintzaras E	Journal of human genetics	2005	PMID: 16172806
Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder.	Lohoff FW	American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics	2005	PMID: 16152572
Linkage disequilibrium of the brain-derived neurotrophic factor Val66Met polymorphism in children with a prepubertal and early adolescent bipolar disorder phenotype.	Geller B	The American journal of psychiatry	2004	PMID: 15337662
Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations.	Ribasés M	Human molecular genetics	2004	PMID: 15115760
Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type.	Ribasés M	Molecular psychiatry	2003	PMID: 12888803
Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder.	Hall D	American journal of human genetics	2003	PMID: 12836135
The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.	Egan MF	Cell	2003	PMID: 12553913
The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study.	Neves-Pereira M	American journal of human genetics	2002	PMID: 12161822
Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor.	Sklar P	Molecular psychiatry	2002	PMID: 12140781
Hamosh, A. Personal Communication. 2018. Baltimore, Md.	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_001709.5(BDNF):c.[*1785G>T;-21-14109C>G196G>A]

Variant Details

NM_001709.5(BDNF):c.[*1785G>T;-21-14109C>G196G>A]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...