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NM_015665.6(AAAS):c.688C>T (p.Arg230Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 28, 2024
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:
RCV001043399.8

Allele description [Variation Report for NM_015665.6(AAAS):c.688C>T (p.Arg230Ter)]

NM_015665.6(AAAS):c.688C>T (p.Arg230Ter)

Gene:
AAAS:aladin WD repeat nucleoporin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_015665.6(AAAS):c.688C>T (p.Arg230Ter)
HGVS:
  • NC_000012.12:g.53314299G>A
  • NG_016775.1:g.12330C>T
  • NM_001173466.2:c.589C>T
  • NM_015665.6:c.688C>TMANE SELECT
  • NP_001166937.1:p.Arg197Ter
  • NP_056480.1:p.Arg230Ter
  • NC_000012.11:g.53708083G>A
  • NM_015665.5:c.688C>T
Protein change:
R197*
Links:
dbSNP: rs758057774
NCBI 1000 Genomes Browser:
rs758057774
Molecular consequence:
  • NM_001173466.2:c.589C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_015665.6:c.688C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001207143Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 28, 2024) 		germlineclinical testing

PubMed (3)
[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

Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.

Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A.

Hum Mol Genet. 2001 Feb 1;10(3):283-90.

PubMed [citation]
PMID:
11159947

Clinical and genetic characterization of families with triple A (Allgrove) syndrome.

Houlden H, Smith S, De Carvalho M, Blake J, Mathias C, Wood NW, Reilly MM.

Brain. 2002 Dec;125(Pt 12):2681-90.

PubMed [citation]
PMID:
12429595
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001207143.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg230*) in the AAAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AAAS are known to be pathogenic (PMID: 11159947). This variant is present in population databases (rs758057774, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Allgrove syndrome (PMID: 12429595). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 841221). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jan 25, 2025