NM_174916.3(UBR1):c.2840-1G>A AND Johanson-Blizzard syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 17, 2014
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004018320.1

Allele description [Variation Report for NM_174916.3(UBR1):c.2840-1G>A]

NM_174916.3(UBR1):c.2840-1G>A

Gene:

UBR1:ubiquitin protein ligase E3 component n-recognin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.2

Genomic location:

Preferred name:

NM_174916.3(UBR1):c.2840-1G>A

HGVS:

NC_000015.10:g.43021376C>T
NG_012182.1:g.89713G>A
NM_174916.3:c.2840-1G>AMANE SELECT
NC_000015.9:g.43313574C>T

Molecular consequence:

NM_174916.3:c.2840-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Johanson-Blizzard syndrome (JBS)
Synonyms:: Nasal alar hypoplasia, hypothyroidism, pancreatic achylia and congenital deafness
Identifiers:: MONDO: MONDO:0009479; MedGen: C0175692; Orphanet: 2315; OMIM: 243800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847513	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Apr 17, 2014)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16311597, 20556423, 21931868, 19058315, 18553553, 19006206, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847513

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Apr 17, 2014)

germline

clinical testing

PubMed (7)
[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

Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome).

Zenker M, Mayerle J, Lerch MM, Tagariello A, Zerres K, Durie PR, Beier M, Hülskamp G, Guzman C, Rehder H, Beemer FA, Hamel B, Vanlieferinghen P, Gershoni-Baruch R, Vieira MW, Dumic M, Auslender R, Gil-da-Silva-Lopes VL, Steinlicht S, Rauh M, Shalev SA, Thiel C, et al.

Nat Genet. 2005 Dec;37(12):1345-50. Epub 2005 Nov 20. Erratum in: Nat Genet. 2006 Feb;38(2):265. Ekici, Arif B [added].

PubMed [citation]

PMID:: 16311597

Novel UBR1 gene mutation in a patient with typical phenotype of Johanson-Blizzard syndrome.

Fallahi GH, Sabbaghian M, Khalili M, Parvaneh N, Zenker M, Rezaei N.

Eur J Pediatr. 2011 Feb;170(2):233-5. doi: 10.1007/s00431-010-1239-y. Epub 2010 Jun 17.

PubMed [citation]

PMID:: 20556423

See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847513.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The 2840-1G>A variant in UBR1 has not been previously reported by our laboratory, in the literature, or in large population studies. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Complete loss of UBR1 function is an established disease mechanism in Johanson-Blizzard syndrome (Zenker 2005, Alkouri 2008, Al-Dosari 2008, Elting 2008, Hwang 2011, Fallahi 2011). In summary, this variant is likely pathogenic, though additional studies are required to fully establish its clinical significance.

#	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: May 7, 2024

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