NM_018082.6(POLR3B):c.2774C>A (p.Pro925Gln) AND Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 4, 2022
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:: RCV000498916.3

Allele description [Variation Report for NM_018082.6(POLR3B):c.2774C>A (p.Pro925Gln)]

NM_018082.6(POLR3B):c.2774C>A (p.Pro925Gln)

Gene:

POLR3B:RNA polymerase III subunit B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.3

Genomic location:

Preferred name:

NM_018082.6(POLR3B):c.2774C>A (p.Pro925Gln)

HGVS:

NC_000012.12:g.106496115C>A
NG_031837.1:g.143458C>A
NM_001160708.2:c.2600C>A
NM_018082.6:c.2774C>AMANE SELECT
NP_001154180.1:p.Pro867Gln
NP_060552.4:p.Pro925Gln
NC_000012.11:g.106889893C>A
NM_018082.5:c.2774C>A

Protein change:

P867Q; PRO925GLN

Links:

OMIM: 614366.0015; dbSNP: rs775141057

NCBI 1000 Genomes Browser:

rs775141057

Molecular consequence:

NM_001160708.2:c.2600C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_018082.6:c.2774C>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

unknown functional consequence

Observations:

Condition(s)

Name:: Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism
Synonyms:: Hypomyelinating leukodystrophy 8, with or without oligodontia and/or hypogonadotropic hypogonadism; LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH HYPODONTIA AND HYPOGONADOTROPIC HYPOGONADISM; Cerebellar hypoplasia with endosteal sclerosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013722; MedGen: C3280644; Orphanet: 85186; Orphanet: 88637; OMIM: 614381

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000492518	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	no assertion criteria provided	Pathogenic	inherited	clinical testing
SCV002102507	OMIM	no assertion criteria provided	Pathogenic (Mar 4, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000492518

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

no assertion criteria provided

Pathogenic

inherited

clinical testing

SCV002102507

OMIM

no assertion criteria provided

Pathogenic
(Mar 4, 2022)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

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	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cerebellar hypoplasia with endosteal sclerosis is a POLR3-related disorder.

Ghoumid J, Petit F, Boute-Benejean O, Frenois F, Cartigny M, Vanlerberghe C, Smol T, Caumes R, de Roux N, Manouvrier-Hanu S.

Eur J Hum Genet. 2017 Aug;25(8):1011-1014. doi: 10.1038/ejhg.2017.73. Epub 2017 Jun 7.

PubMed [citation]

PMID:: 28589944
PMCID:: PMC5567146

Details of each submission

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV000492518.1

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

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

From OMIM, SCV002102507.1

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

Description

For discussion of the c.2774C-A transversion (c.2774C-A, NM_018082.5) in the POLR3B gene, resulting in a pro925-to-gln (P925Q) substitution, that was found in compound heterozygous state in a patient with hypomyelinating leukodystrophy-8 with hypodontia and hypogonadotropic hypogonadism (HLD8; 614381) by Ghoumid et al. (2017), see 614366.0005.

#	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: Jun 23, 2024

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