NM_002087.4(GRN):c.55C>T (p.Arg19Trp) AND GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

Germline classification:: Benign (2 submissions)
Last evaluated:: Jan 13, 2018
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:: RCV000576325.13

Allele description [Variation Report for NM_002087.4(GRN):c.55C>T (p.Arg19Trp)]

NM_002087.4(GRN):c.55C>T (p.Arg19Trp)

Gene:

GRN:granulin precursor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_002087.4(GRN):c.55C>T (p.Arg19Trp)

HGVS:

NC_000017.11:g.44349219C>T
NG_007886.1:g.9097C>T
NM_002087.4:c.55C>TMANE SELECT
NP_002078.1:p.Arg19Trp
NP_002078.1:p.Arg19Trp
LRG_661t1:c.55C>T
LRG_661:g.9097C>T
NC_000017.10:g.42426587C>T
NM_002087.2:c.55C>T
NM_002087.3:c.55C>T
P28799:p.Arg19Trp

Protein change:

R19W

Links:

UniProtKB: P28799#VAR_064625; dbSNP: rs63750723

NCBI 1000 Genomes Browser:

rs63750723

Molecular consequence:

NM_002087.4:c.55C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
Synonyms:: FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS; FTLD-TDP, GRN-RELATED; Frontotemporal dementia, ubiquitin-positive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011842; MedGen: C1843792; Orphanet: 100070; Orphanet: 282; OMIM: 607485

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000403337	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000677381	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Jun 20, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16950801, 17371905, 19158106, 19632744, 20020531, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000403337

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV000677381

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Benign
(Jun 20, 2017)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration.

Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M, Adamson J, Crook R, Melquist S, Kuntz K, Petersen R, Josephs K, Pickering-Brown SM, Graff-Radford N, Uitti R, Dickson D, Wszolek Z, Gonzalez J, Beach TG, Bigio E, Johnson N, Weintraub S, Mesulam M, et al.

Hum Mol Genet. 2006 Oct 15;15(20):2988-3001. Epub 2006 Sep 1.

PubMed [citation]

PMID:: 16950801

Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes.

Schymick JC, Yang Y, Andersen PM, Vonsattel JP, Greenway M, Momeni P, Elder J, Chiò A, Restagno G, Robberecht W, Dahlberg C, Mukherjee O, Goate A, Graff-Radford N, Caselli RJ, Hutton M, Gass J, Cannon A, Rademakers R, Singleton AB, Hardiman O, Rothstein J, et al.

J Neurol Neurosurg Psychiatry. 2007 Jul;78(7):754-6. Epub 2007 Mar 19.

PubMed [citation]

PMID:: 17371905
PMCID:: PMC2117704

See all PubMed Citations (6)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000403337.3

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

Description

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.

#	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

From Athena Diagnostics, SCV000677381.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

#	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: Jun 9, 2024

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