NM_001375808.2(LPIN2):c.469C>T (p.Arg157Ter) AND Majeed syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 28, 2023
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:: RCV000661951.5

Allele description [Variation Report for NM_001375808.2(LPIN2):c.469C>T (p.Arg157Ter)]

NM_001375808.2(LPIN2):c.469C>T (p.Arg157Ter)

Gene:

LPIN2:lipin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.31

Genomic location:

Preferred name:

NM_001375808.2(LPIN2):c.469C>T (p.Arg157Ter)

HGVS:

NC_000018.10:g.2951176G>A
NG_007507.1:g.65772C>T
NM_001375808.2:c.469C>TMANE SELECT
NM_001375809.1:c.469C>T
NM_014646.2:c.469C>T
NP_001362737.1:p.Arg157Ter
NP_001362738.1:p.Arg157Ter
NP_055461.1:p.Arg157Ter
LRG_174t1:c.469C>T
LRG_174:g.65772C>T
LRG_174p1:p.Arg157Ter
NC_000018.9:g.2951174G>A

Protein change:

R157*

Links:

dbSNP: rs916009547

NCBI 1000 Genomes Browser:

rs916009547

Molecular consequence:

NM_001375808.2:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001375809.1:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014646.2:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Majeed syndrome (MJDS)
Synonyms:: Chronic recurrent multifocal osteomyelitis, congenital; Dyserythropoietic anemia, and neutrophilic dermatosis; Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012316; MedGen: C1864997; Orphanet: 77297; OMIM: 609628

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000784281	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 5, 2018)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004644877	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15994876, 23087183, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000784281

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 5, 2018)

inherited

clinical testing

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

SCV004644877

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2023)

germline

clinical testing

PubMed (3)
[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
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome).

Ferguson PJ, Chen S, Tayeh MK, Ochoa L, Leal SM, Pelet A, Munnich A, Lyonnet S, Majeed HA, El-Shanti H.

J Med Genet. 2005 Jul;42(7):551-7.

PubMed [citation]

PMID:: 15994876
PMCID:: PMC1736104

See all PubMed Citations (4)

Details of each submission

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000784281.2

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

#	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 Invitae, SCV004644877.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg157*) in the LPIN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LPIN2 are known to be pathogenic (PMID: 15994876, 23087183). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LPIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 548484). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2024

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