NM_005211.3(CSF1R):c.2345G>A (p.Arg782His) AND Hereditary diffuse leukoencephalopathy with spheroids

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 12, 2013
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000031932.4

Allele description

NM_005211.3(CSF1R):c.2345G>A (p.Arg782His)

Gene:

CSF1R:colony stimulating factor 1 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_005211.3(CSF1R):c.2345G>A (p.Arg782His)

HGVS:

NC_000005.10:g.150056316C>T
NG_012303.1:g.62057G>A
NM_005211.3:c.2345G>A
NP_005202.2:p.Arg782His
NC_000005.9:g.149435879C>T
NR_109969.1:n.2395G>A

Protein change:

R782H; ARG782HIS

Links:

OMIM: 164770.0009; dbSNP: rs281860281

NCBI 1000 Genomes Browser:

rs281860281

Molecular consequence:

NM_005211.3:c.2345G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_109969.1:n.2395G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary diffuse leukoencephalopathy with spheroids (HDLS)
Synonyms:: DEMENTIA, FAMILIAL, NEUMANN TYPE; SUBCORTICAL GLIOSIS OF NEUMANN; Gliosis, familial progressive subcortical; See all synonyms [MedGen]
Identifiers:: Gene: 8156; MedGen: C3711381; Orphanet: 313808; OMIM: 221820

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000054585	GeneReviews	no assertion criteria provided	pathologic (Aug 30, 2012)	not provided	curation
SCV000191969	OMIM	no assertion criteria provided	Pathogenic (Mar 12, 2013)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8614507, 23408870

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000054585

GeneReviews

no assertion criteria provided

pathologic
(Aug 30, 2012)

not provided

curation

SCV000191969

OMIM

no assertion criteria provided

Pathogenic
(Mar 12, 2013)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Progressive familial leukodystrophy of late onset.

Knopman D, Sung JH, Davis D.

Neurology. 1996 Feb;46(2):429-34.

PubMed [citation]

PMID:: 8614507

CSF1R mutations link POLD and HDLS as a single disease entity.

Nicholson AM, Baker MC, Finch NA, Rutherford NJ, Wider C, Graff-Radford NR, Nelson PT, Clark HB, Wszolek ZK, Dickson DW, Knopman DS, Rademakers R.

Neurology. 2013 Mar 12;80(11):1033-40. doi: 10.1212/WNL.0b013e31828726a7. Epub 2013 Feb 13.

PubMed [citation]

PMID:: 23408870
PMCID:: PMC3653204

Details of each submission

From GeneReviews, SCV000054585.1

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

Description

Converted during submission to Pathogenic.

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

From OMIM, SCV000191969.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of a family (FTD368) with HDLS (221820), originally reported by Knopman et al. (1996), Nicholson et al. (2013) identified a heterozygous c.2345G-A transition in exon 18 of the CSF1R gene, resulting in an arg782-to-his (R782H) substitution in the kinase domain. The mutation segregated with the disorder in the family and was not found in 1,089 white, non-Hispanic control individuals. In vitro functional expression studies in HeLa cells showed that the R782H mutation abrogated CSF1R autophosphorylation, which would inhibit downstream signaling. Since the family had originally received a clinicopathologic diagnosis of pigmented orthochromatic leukodystrophy (POLD), the findings indicated that POLD and HDLS are a single disease entity.

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

Last Updated: Jul 21, 2018

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