NM_001081.4(CUBN):c.2614_2615del (p.Asp872fs) AND Imerslund-Gräsbeck syndrome 1

Clinical significance:Pathogenic (Last evaluated: May 18, 2020)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001095373.1

Allele description [Variation Report for NM_001081.4(CUBN):c.2614_2615del (p.Asp872fs)]

NM_001081.4(CUBN):c.2614_2615del (p.Asp872fs)

Gene:
CUBN:cubilin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001081.4(CUBN):c.2614_2615del (p.Asp872fs)
HGVS:
  • NC_000010.11:g.17071437_17071438del
  • NG_008967.1:g.63381_63382del
  • NM_001081.4:c.2614_2615delMANE SELECT
  • NP_001072.2:p.Asp872fs
  • LRG_540:g.63381_63382del
  • NC_000010.10:g.17113436_17113437del
  • NM_001081.3:c.2614_2615delGA
Protein change:
D872fs
Links:
OMIM: 602997.0006; dbSNP: rs386833777
NCBI 1000 Genomes Browser:
rs386833777
Molecular consequence:
  • NM_001081.4:c.2614_2615del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Imerslund-Gräsbeck syndrome 1 (IGS1)
Synonyms:
Megaloblastic anemia 1, Finnish type; MEGALOBLASTIC ANEMIA, FINNISH TYPE
Identifiers:
MONDO: MONDO:0100156; MedGen: C4016819; OMIM: 261100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001250981OMIMno assertion criteria providedPathogenic
(May 18, 2020)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Profound vitamin D deficiency in four siblings with Imerslund-Grasbeck syndrome with homozygous CUBN mutation.

Ciancio JIR, Furman M, Banka S, Grunewald S.

JIMD Rep. 2019 Sep;49(1):43-47. doi: 10.1002/jmd2.12072.

PubMed [citation]
PMID:
31497480
PMCID:
PMC6718117

Details of each submission

From OMIM, SCV001250981.15

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 4 sibs, born of unrelated parents of Ashkenazi Jewish background, with Imerslund-Grasbeck syndrome-1 (IGS1; 261100), Ciancio et al. (2019) identified a homozygous 2-bp deletion (c.2614_2615delGA, NM_001081.3) in the CUBN gene, resulting in a frameshift and premature termination (Asp872LeufsTer3). The mutation was predicted to result in nonsense-mediated mRNA decay and complete loss of the CUBN protein. In addition, all patients had profound vitamin D deficiency requiring supplementation. Ciancio et al. (2019) concluded that null CUBN mutations may affect absorption of the VDBP protein, resulting in vitamin D deficiency; this suggested a possible genotype/phenotype correlation. Functional studies of the variant and studies of patient cells were not performed. The authors stated that this mutation is a founder mutation in the Ashkenazi Jewish population.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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