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NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 16, 2019
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:
RCV002427053.2

Allele description [Variation Report for NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys)]

NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys)

Gene:
MEN1:menin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.1
Genomic location:
Preferred name:
NM_001370259.2(MEN1):c.824G>A (p.Arg275Lys)
HGVS:
  • NC_000011.10:g.64807179C>T
  • NG_008929.1:g.9116G>A
  • NG_033040.1:g.1063G>A
  • NM_000244.4:c.839G>A
  • NM_001370251.2:c.824G>A
  • NM_001370259.2:c.824G>AMANE SELECT
  • NM_001370260.2:c.824G>A
  • NM_001370261.2:c.824G>A
  • NM_001370262.2:c.719G>A
  • NM_001370263.2:c.719G>A
  • NM_130799.3:c.824G>A
  • NM_130800.3:c.839G>A
  • NM_130801.3:c.839G>A
  • NM_130802.3:c.839G>A
  • NM_130803.3:c.839G>A
  • NM_130804.3:c.839G>A
  • NP_000235.3:p.Arg280Lys
  • NP_001357180.2:p.Arg275Lys
  • NP_001357188.2:p.Arg275Lys
  • NP_001357189.2:p.Arg275Lys
  • NP_001357190.2:p.Arg275Lys
  • NP_001357191.2:p.Arg240Lys
  • NP_001357192.2:p.Arg240Lys
  • NP_570711.1:p.Arg275Lys
  • NP_570711.2:p.Arg275Lys
  • NP_570712.2:p.Arg280Lys
  • NP_570713.2:p.Arg280Lys
  • NP_570714.2:p.Arg280Lys
  • NP_570715.2:p.Arg280Lys
  • NP_570716.2:p.Arg280Lys
  • LRG_509t2:c.824G>A
  • LRG_509:g.9116G>A
  • LRG_509p2:p.Arg275Lys
  • NC_000011.9:g.64574651C>T
  • NM_130799.2:c.824G>A
Protein change:
R240K
Links:
dbSNP: rs1187634059
NCBI 1000 Genomes Browser:
rs1187634059
Molecular consequence:
  • NM_000244.4:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370251.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370259.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370260.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370261.2:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370262.2:c.719G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370263.2:c.719G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130799.3:c.824G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130800.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130801.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130802.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130803.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130804.3:c.839G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002681024Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 16, 2019) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A MEN1 syndrome with a paraganglioma.

Jamilloux Y, Favier J, Pertuit M, Delage-Corre M, Lopez S, Teissier MP, Mathonnet M, Galinat S, Barlier A, Archambeaud F.

Eur J Hum Genet. 2014 Feb;22(2):283-5. doi: 10.1038/ejhg.2013.128. Epub 2013 Jun 19.

PubMed [citation]
PMID:
23778871
PMCID:
PMC3895646

Details of each submission

From Ambry Genetics, SCV002681024.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The c.824G>A pathogenic mutation (also known as p.R275K), located in coding exon 4 of the MEN1 gene, results from a G to A substitution at nucleotide position 824. The amino acid change results in arginine to lysine at codon 275, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 4, which makes it likely to have some effect on normal mRNA splicing. This alteration was identified in a proband meeting diagnostic criteria for multiple endocrine neoplasia type 1 (MEN1) who presented with parathyroid hyperplasia, adrenal adenoma, and a pancreatic endocrine tumor, as well as an extra-adrenal paraganglioma. Her sister was also positive for c.824G>A and presented with hyperparathyroidism and multiple pancreatic neuroendocrine tumors (Jamilloux Y et al. Eur. J. Hum. Genet., 2014 Feb;22:283-5). This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by BDGP; however, direct evidence is unavailable. In addition, c.824G>A was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024