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

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Sep 30, 2021)
Last evaluated:
Feb 27, 2020
Accession:
VCV000449954.9
Variation ID:
449954
Description:
single nucleotide variant
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NM_017849.4(TMEM127):c.410-2A>G

Allele ID
443319
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q11.2
Genomic location
2: 96254117 (GRCh38) GRCh38 UCSC
2: 96919855 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_528:g.16897A>G
LRG_528t1:c.410-2A>G
NC_000002.11:g.96919855T>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000002.12:96254116:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA347653204
dbSNP: rs121908826
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, single submitter May 1, 2017 RCV000519103.3
Likely pathogenic 1 criteria provided, single submitter Feb 27, 2020 RCV000699788.4
Likely pathogenic 1 criteria provided, single submitter Dec 12, 2018 RCV001021873.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TMEM127 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
473 531

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(May 01, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000618440.2
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted TMEM127 c.410-2A>G or IVS3-2A>G and consists of an A>G nucleotidesubstitution at the -2 position of intron 3 of the TMEM127 gene. … (more)
Likely pathogenic
(Feb 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary Paraganglioma-Pheochromocytoma Syndromes
Allele origin: germline
Invitae
Accession: SCV000828515.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change affects an acceptor splice site in the last intron (intron 3) of the TMEM127 gene. While this is not anticipated to result … (more)
Likely pathogenic
(Dec 12, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV001183542.2
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
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 … (more)
Likely pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931668.1
Submitted: (Sep 23, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951392.1
Submitted: (Sep 30, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Homozygous TMEM127 mutations in 2 patients with bilateral pheochromocytomas. Eijkelenkamp K Clinical genetics 2018 PMID: 29282712
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Penetrance and clinical features of pheochromocytoma in a six-generation family carrying a germline TMEM127 mutation. Toledo SP The Journal of clinical endocrinology and metabolism 2015 PMID: 25389632
Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas. Yao L JAMA 2010 PMID: 21156949
Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Qin Y Nature genetics 2010 PMID: 20154675
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098

Text-mined citations for rs121908826...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 24, 2021