VCV000098211.15 - ClinVar

NM_001377265.1(MAPT):c.1986G>A (p.Pro662=)

Interpretation:: Benign
Review status:: criteria provided, multiple submitters, no conflicts
Submissions:: 10
First in ClinVar:: Feb 20, 2014
Most recent Submission:: May 16, 2022
Last evaluated:: Dec 18, 2021
Accession:: VCV000098211.15
Variation ID:: 98211
Description:: single nucleotide variant

NM_001377265.1(MAPT):c.1986G>A (p.Pro662=)

Allele ID

104103

Variant type

single nucleotide variant

Variant length

1 bp

Cytogenetic location

17q21.31

Genomic location

17: 45996652 (GRCh38) GRCh38 UCSC

17: 44074018 (GRCh37) GRCh37 UCSC

HGVS

Nucleotide	Protein	Molecular consequence
NM_001377265.1:c.1986G>A MANE Select	NP_001364194.1:p.Pro662=	synonymous
NM_001123066.4:c.1815G>A	NP_001116538.2:p.Pro605=	synonymous
NM_001123067.4:c.723G>A	NP_001116539.1:p.Pro241=	synonymous
NM_001203251.2:c.723G>A	NP_001190180.1:p.Pro241=	synonymous
NM_001203252.2:c.810G>A	NP_001190181.1:p.Pro270=	synonymous
NM_001377266.1:c.1788G>A	NP_001364195.1:p.Pro596=	synonymous
NM_001377267.1:c.723G>A	NP_001364196.1:p.Pro241=	synonymous
NM_001377268.1:c.636G>A	NP_001364197.1:p.Pro212=	synonymous
NM_005910.6:c.810G>A	NP_005901.2:p.Pro270=	synonymous
NM_016834.5:c.636G>A	NP_058518.1:p.Pro212=	synonymous
NM_016835.5:c.1761G>A	NP_058519.3:p.Pro587=	synonymous
NM_016841.5:c.636G>A	NP_058525.1:p.Pro212=	synonymous
NR_165166.1:n.734G>A
NC_000017.11:g.45996652G>A
NC_000017.10:g.44074018G>A
NG_007398.1:g.107232G>A
NG_007398.2:g.107190G>A
LRG_660:g.107190G>A
LRG_660t1:c.1761G>A	LRG_660p1:p.Pro587=
LRG_660t2:c.1986G>A	LRG_660p2:p.Pro662=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:45996651:G:A

Functional consequence

Global minor allele frequency (GMAF)

0.03295 (A)

Allele frequency

Exome Aggregation Consortium (ExAC) 0.03595

The Genome Aggregation Database (gnomAD) 0.03713

1000 Genomes Project 0.03295

The Genome Aggregation Database (gnomAD) 0.03866

The Genome Aggregation Database (gnomAD), exomes 0.03521

Trans-Omics for Precision Medicine (TOPMed) 0.03889

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.04306

Links

ClinGen: CA225419

dbSNP: rs11568305

VarSome

Aggregate interpretations per condition

Interpreted condition	Interpretation	Number of submissions	Review status	Last evaluated	Variation/condition record
not specified	Benign	6	criteria provided, multiple submitters, no conflicts	Feb 25, 2011	RCV000253733.5
not provided	Benign	2	criteria provided, single submitter	Sep 8, 2021	RCV000084518.5
MAPT-Related Spectrum Disorders	Benign	1	criteria provided, single submitter	Jan 13, 2018	RCV000347983.3
Frontotemporal dementia	Benign	1	criteria provided, single submitter	Dec 18, 2021	RCV000554260.6

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation viewer	Related variants
Gene	OMIM	HI score Help	TS score Help	Variation viewer	Within gene	All
MAPT		No evidence available	No evidence available	GRCh38 GRCh38 GRCh38 GRCh37	390	515

Submitted interpretations and evidence

Interpretation (Last evaluated)	Review status (Assertion criteria)	Condition (Inheritance)	Submitter	More information
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics,PreventionGenetics Accession: SCV000306672.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Feb 25, 2011)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Athena Diagnostics Inc Accession: SCV000614048.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Publications: PubMed (4) PubMed: 9973279‚ 19091059‚ 18854867‚ 25671699
Benign (Sep 08, 2021)	criteria provided, single submitter (GeneDX Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001802690.2 First in ClinVar: Aug 21, 2021 Last updated: Nov 06, 2021	Comment: This variant is associated with the following publications: (PMID: 12826737, 26159191, 18854867, 19091059, 9973279, 20020531, 16410051, 25671699)
Benign (Dec 18, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Frontotemporal dementia Affected status: unknown Allele origin: germline	Invitae Accession: SCV000632353.4 First in ClinVar: Dec 26, 2017 Last updated: May 16, 2022
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	MAPT-Related Spectrum Disorders Affected status: unknown Allele origin: germline	Illumina Laboratory Services,Illumina Accession: SCV000403488.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001932705.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001808623.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001922507.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001970438.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
not provided (-)	no assertion provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	VIB Department of Molecular Genetics, University of Antwerp Accession: SCV000116654.1 First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014 Comment: http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg18&id=ADM_222

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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 this variant

Title	Author	Journal	Year	Link
Pooled sequencing of 531 genes in inflammatory bowel disease identifies an associated rare variant in BTNL2 and implicates other immune related genes.	Prescott NJ	PLoS genetics	2015	PMID: 25671699
H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers.	Canu E	European journal of human genetics : EJHG	2009	PMID: 18854867
Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland.	Kaivorinne AL	BMC neurology	2008	PMID: 19091059
High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands.	Rizzu P	American journal of human genetics	1999	PMID: 9973279

Text-mined citations for rs11568305...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 24, 2022

ClinVar Genomic variation as it relates to human health

NM_001377265.1(MAPT):c.1986G>A (p.Pro662=)

NM_001377265.1(MAPT):c.1986G>A (p.Pro662=)

Aggregate interpretations per condition

Submitted interpretations and evidence

Functional evidence

Citations for this variant

Text-mined citations for rs11568305...