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NM_033629.6(TREX1):c.52G>A (p.Asp18Asn) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 1, 2023
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:
RCV000819829.14

Allele description [Variation Report for NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)]

NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)

Genes:
ATRIP:ATR interacting protein [Gene - OMIM - HGNC]
ATRIP-TREX1:ATRIP-TREX1 readthrough [Gene]
TREX1:three prime repair exonuclease 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)
HGVS:
  • NC_000003.12:g.48466707G>A
  • NG_009820.2:g.5878G>A
  • NG_033100.1:g.39154C>T
  • NG_033100.2:g.43103C>T
  • NG_041782.1:g.24998G>A
  • NG_099339.1:g.650G>A
  • NM_001271022.2:c.*1153G>A
  • NM_001271023.2:c.*1153G>A
  • NM_007248.5:c.22G>A
  • NM_032166.4:c.*1153G>A
  • NM_033629.6:c.52G>AMANE SELECT
  • NM_130384.3:c.*1153G>AMANE SELECT
  • NP_009179.2:p.Asp8Asn
  • NP_338599.1:p.Asp18Asn
  • NP_338599.1:p.Asp18Asn
  • LRG_282t1:c.52G>A
  • AAK07616.1:p.Asp18Asn
  • AF319569.1:c.52G>A
  • LRG_282:g.5878G>A
  • LRG_282p1:p.Asp18Asn
  • NC_000003.11:g.48508106G>A
  • NM_033629.2:c.52G>A
  • NM_033629.4:c.52G>A
  • NR_153405.1:n.3361G>A
  • Q9NSU2:p.Asp73Asn
Protein change:
D18N; ASP18ASN
Links:
UniProtKB: Q9NSU2#VAR_037948; OMIM: 606609.0007; dbSNP: rs121908117
NCBI 1000 Genomes Browser:
rs121908117
Molecular consequence:
  • NM_001271022.2:c.*1153G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001271023.2:c.*1153G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_032166.4:c.*1153G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_130384.3:c.*1153G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_007248.5:c.22G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033629.6:c.52G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_153405.1:n.3361G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Aicardi-Goutieres syndrome 1
Synonyms:
CREE ENCEPHALITIS; ENCEPHALOPATHY, FAMILIAL INFANTILE, WITH INTRACRANIAL CALCIFICATION AND CHRONIC CEREBROSPINAL FLUID LYMPHOCYTOSIS; PSEUDOTOXOPLASMOSIS SYNDROME
Identifiers:
MONDO: MONDO:0009165; MedGen: C0796126; Orphanet: 51; OMIM: 225750
Name:
Chilblain lupus 1 (CHBL1)
Identifiers:
MONDO: MONDO:0012500; MedGen: C0024145; OMIM: 610448
Name:
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS)
Synonyms:
Vasculopathy, retinal, with cerebral leukodystrophy; Cerebroretinal vasculopathy, hereditary; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena
Identifiers:
MONDO: MONDO:0008641; MedGen: C1860518; Orphanet: 3421; Orphanet: 63261; Orphanet: 71291; OMIM: 192315

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000960511Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 1, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutières syndrome.

Haaxma CA, Crow YJ, van Steensel MA, Lammens MM, Rice GI, Verbeek MM, Willemsen MA.

Am J Med Genet A. 2010 Oct;152A(10):2612-7. doi: 10.1002/ajmg.a.33620.

PubMed [citation]
PMID:
20799324

Heterozygous TREX1 p.Asp18Asn mutation can cause variable neurological symptoms in a family with Aicardi-Goutieres syndrome/familial chilblain lupus.

Abe J, Izawa K, Nishikomori R, Awaya T, Kawai T, Yasumi T, Hiragi N, Hiragi T, Ohshima Y, Heike T.

Rheumatology (Oxford). 2013 Feb;52(2):406-8. doi: 10.1093/rheumatology/kes181. Epub 2012 Jul 23. No abstract available.

PubMed [citation]
PMID:
22829693
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960511.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This missense change has been observed in individual(s) with Aicardi-Goutieres syndrome (PMID: 17440703, 20799324, 22829693, 23989343). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4185). 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 TREX1 function (PMID: 17440703, 18805785, 20871604, 25848017). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 18 of the TREX1 protein (p.Asp18Asn).

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

Last Updated: Oct 26, 2024