ClinVar Genomic variation as it relates to human health
NM_000447.3(PSEN2):c.211C>T (p.Arg71Trp)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000447.3(PSEN2):c.211C>T (p.Arg71Trp)
Variation ID: 192130 Accession: VCV000192130.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q42.13 1: 226883774 (GRCh38) [ NCBI UCSC ] 1: 227071475 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 14, 2015 Feb 20, 2024 Jan 13, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000447.3:c.211C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000438.2:p.Arg71Trp missense NM_012486.3:c.211C>T NP_036618.2:p.Arg71Trp missense NC_000001.11:g.226883774C>T NC_000001.10:g.227071475C>T NG_007381.2:g.18591C>T LRG_225:g.18591C>T LRG_225t1:c.211C>T LRG_225p1:p.Arg71Trp P49810:p.Arg71Trp - Protein change
- R71W
- Other names
- -
- Canonical SPDI
- NC_000001.11:226883773:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00140 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00140
1000 Genomes Project 30x 0.00156
Trans-Omics for Precision Medicine (TOPMed) 0.00187
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00277
Exome Aggregation Consortium (ExAC) 0.00336
The Genome Aggregation Database (gnomAD) 0.00349
The Genome Aggregation Database (gnomAD), exomes 0.00357
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 | ||
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HI score
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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. |
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PSEN2 | - | - |
GRCh38 GRCh37 |
275 | 318 |
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. |
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Likely benign (1) |
criteria provided, single submitter
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Jun 24, 2013 | RCV000172587.5 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Sep 18, 2023 | RCV000861064.8 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 13, 2024 | RCV000986559.13 | |
Benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001099114.5 |
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. |
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Likely benign
(Nov 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000614831.2
First in ClinVar: Sep 14, 2015 Last updated: Jan 18, 2020 |
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Benign
(Jan 13, 2024)
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criteria provided, single submitter
Method: clinical testing
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Alzheimer disease 4
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001001275.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004563098.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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Likely benign
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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not specified
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000051420.2 First in ClinVar: Jun 04, 2015 Last updated: Sep 14, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
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Number of individuals with the variant: 4
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Alzheimer disease 4
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001135578.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1V
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001255535.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Alzheimer disease 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001253646.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927747.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807919.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. | Nicolas G | European journal of human genetics : EJHG | 2016 | PMID: 26242991 |
Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease. | Schulte EC | European journal of human genetics : EJHG | 2015 | PMID: 25604855 |
The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-ε4 carriers. | Benitez BA | PLoS genetics | 2013 | PMID: 23990795 |
RNAi-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion and is involved in the regulation of Nrg1/ErbB signaling. | Liu B | Neuro-oncology | 2012 | PMID: 22753229 |
Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients. | Lohmann E | Neurobiology of aging | 2012 | PMID: 22503161 |
The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. | Wallon D | Journal of Alzheimer's disease : JAD | 2012 | PMID: 22475797 |
Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. | Cruchaga C | PloS one | 2012 | PMID: 22312439 |
DLB and PDD: a role for mutations in dementia and Parkinson disease genes? | Meeus B | Neurobiology of aging | 2012 | PMID: 22118943 |
Molecular genetic analysis of the APP, PSEN1, and PSEN2 genes in Finnish patients with early-onset Alzheimer disease and frontotemporal lobar degeneration. | Krüger J | Alzheimer disease and associated disorders | 2012 | PMID: 21959359 |
Presenilin 2 mutation R71W in an Italian early-onset sporadic Alzheimer's disease case. | Piscopo P | Journal of neurology | 2011 | PMID: 21544564 |
Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. | Guerreiro RJ | Neurobiology of aging | 2010 | PMID: 18667258 |
Functional characterization of novel presenilin-2 variants identified in human breast cancers. | To MD | Oncogene | 2006 | PMID: 16474849 |
Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. | Sleegers K | Brain : a journal of neurology | 2004 | PMID: 15130954 |
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Text-mined citations for rs140501902 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.