NM_017849.4(TMEM127):c.410-2A>G AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Dec 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001021873.1

Allele description [Variation Report for NM_017849.4(TMEM127):c.410-2A>G]

NM_017849.4(TMEM127):c.410-2A>G

Gene:
TMEM127:transmembrane protein 127 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q11.2
Genomic location:
Preferred name:
NM_017849.4(TMEM127):c.410-2A>G
HGVS:
  • NC_000002.12:g.96254117T>C
  • NG_027695.1:g.16897A>G
  • NM_001193304.3:c.410-2A>G
  • NM_017849.3:c.410-2A>G
  • NM_017849.4:c.410-2A>GMANE SELECT
  • LRG_528t1:c.410-2A>G
  • LRG_528:g.16897A>G
  • NC_000002.11:g.96919855T>C
  • NC_000002.11:g.96919855T>C
Links:
dbSNP: rs121908826
NCBI 1000 Genomes Browser:
rs121908826
Molecular consequence:
  • NM_001193304.3:c.410-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_017849.3:c.410-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_017849.4:c.410-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001183542Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Dec 12, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Homozygous TMEM127 mutations in 2 patients with bilateral pheochromocytomas.

Eijkelenkamp K, Olderode-Berends MJW, van der Luijt RB, Robledo M, van Dooren M, Feelders RA, de Vries J, Kerstens MN, Links TP, van der Horst-Schrivers ANA.

Clin Genet. 2018 May;93(5):1049-1056. doi: 10.1111/cge.13202. Epub 2018 Mar 23.

PubMed [citation]
PMID:
29282712

Details of each submission

From Ambry Genetics, SCV001183542.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The c.410-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 3 in the TMEM127 gene. This mutation has been reported in a homozygous state in an individual diagnosed with bilateral pheochromocytoma at age 31 as well as dysmorphic features and intellectual disability (Eijkelenkamp K et al. Clin. Genet., 2018 May;93:1049-1056). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2021

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