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NM_001143992.2(WRAP53):c.1192C>T (p.Arg398Trp) AND not provided

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Jan 10, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV001269522.10

Allele description [Variation Report for NM_001143992.2(WRAP53):c.1192C>T (p.Arg398Trp)]

NM_001143992.2(WRAP53):c.1192C>T (p.Arg398Trp)

Gene:
WRAP53:WD repeat containing antisense to TP53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_001143992.2(WRAP53):c.1192C>T (p.Arg398Trp)
HGVS:
  • NC_000017.11:g.7702770C>T
  • NG_028245.1:g.21700C>T
  • NM_001143990.2:c.1192C>T
  • NM_001143991.2:c.1192C>T
  • NM_001143992.2:c.1192C>TMANE SELECT
  • NM_018081.2:c.1192C>T
  • NP_001137462.1:p.Arg398Trp
  • NP_001137463.1:p.Arg398Trp
  • NP_001137464.1:p.Arg398Trp
  • NP_060551.2:p.Arg398Trp
  • LRG_375t1:c.1192C>T
  • LRG_375:g.21700C>T
  • LRG_375p1:p.Arg398Trp
  • NC_000017.10:g.7606088C>T
  • NM_001143990.1:c.1192C>T
  • Q9BUR4:p.Arg398Trp
Protein change:
R398W; ARG398TRP
Links:
UniProtKB: Q9BUR4#VAR_065875; OMIM: 612661.0002; dbSNP: rs281865548
NCBI 1000 Genomes Browser:
rs281865548
Molecular consequence:
  • NM_001143990.2:c.1192C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001143991.2:c.1192C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001143992.2:c.1192C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018081.2:c.1192C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001449566Clinical Genetics and Genomics, Karolinska University Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jan 29, 2015)
germlineclinical testing

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

SCV001536251Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 10, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita.

Zhong F, Savage SA, Shkreli M, Giri N, Jessop L, Myers T, Chen R, Alter BP, Artandi SE.

Genes Dev. 2011 Jan 1;25(1):11-6. doi: 10.1101/gad.2006411.

PubMed [citation]
PMID:
21205863
PMCID:
PMC3012932
See all PubMed Citations (4)

Details of each submission

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449566.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001536251.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 398 of the WRAP53 protein (p.Arg398Trp). This variant is present in population databases (rs281865548, gnomAD 0.3%). This missense change has been observed in individual(s) with clinical features of Hoyeraal Hreidarsson syndrome or dyskeratosis congenita (PMID: 21205863, 32303682). ClinVar contains an entry for this variant (Variation ID: 30975). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects WRAP53 function (PMID: 21205863, 32303682). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 7, 2025