NM_000383.4(AIRE):c.769C>T (p.Arg257Ter) AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jul 31, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000378770.34

Allele description [Variation Report for NM_000383.4(AIRE):c.769C>T (p.Arg257Ter)]

NM_000383.4(AIRE):c.769C>T (p.Arg257Ter)

Gene:

AIRE:autoimmune regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_000383.4(AIRE):c.769C>T (p.Arg257Ter)

HGVS:

NC_000021.9:g.44289773C>T
NG_009556.1:g.8894C>T
NM_000383.4:c.769C>TMANE SELECT
NP_000374.1:p.Arg257Ter
LRG_18t1:c.769C>T
LRG_18:g.8894C>T
LRG_18p1:p.Arg257Ter
NC_000021.8:g.45709656C>T
NM_000383.2:c.769C>T
NM_000383.3:c.769C>T

Protein change:

R257*; ARG257TER

Links:

OMIM: 607358.0001; dbSNP: rs121434254

NCBI 1000 Genomes Browser:

rs121434254

Molecular consequence:

NM_000383.4:c.769C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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microtubule-associated serine/threonine-protein kinase 2 isoform X26 [Homo sapie...
microtubule-associated serine/threonine-protein kinase 2 isoform X26 [Homo sapiens]
gi|2462506597|ref|XP_054191329.1|

Protein
Taxonomy Links for GEO Profiles (Select 101677630) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000231520	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 14, 2014)	germline	clinical testing	Citation Link,
SCV000329055	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 17, 2022)	germline	clinical testing	Citation Link,
SCV000840731	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (May 23, 2018)	germline	clinical testing	PubMed (24) [See all records that cite these PMIDs] 10677297, 11343230, 11524733, 12503856, 12843157, 14582926, 16313305, 16684821, 16784312, 17118990, 17289071, 18248641, 18264745, 18274776, 18320920, 18426830, 18616706, 18682433, 19037923, 19246027, 20718774, 9398839, 9398840, 26467025
SCV001247536	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2024)	germline	clinical testing	Citation Link,
SCV001978034	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001980556	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV005089747	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein.

Björses P, Halonen M, Palvimo JJ, Kolmer M, Aaltonen J, Ellonen P, Perheentupa J, Ulmanen I, Peltonen L.

Am J Hum Genet. 2000 Feb;66(2):378-92.

PubMed [citation]

PMID:: 10677297
PMCID:: PMC1288090

Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1.

Vogel A, Liermann H, Harms A, Strassburg CP, Manns MP, Obermayer-Straub P.

Hepatology. 2001 May;33(5):1047-52.

PubMed [citation]

PMID:: 11343230

See all PubMed Citations (25)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000231520.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV000329055.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate lack of expression of mRNA from AIRE-dependent genes (Oftedal et al., 2015); R257X variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations (Finnish-German APECED Consortium 1997; Heino et al., 2001); This variant is associated with the following publications: (PMID: 22162465, 20718774, 24948345, 16965330, 11524733, 15886230, 11524731, 11298085, 22024611, 18616706, 9921903, 19807739, 12050215, 19863576, 25707324, 27065010, 27048654, 26891119, 14582926, 24158785, 18274776, 28458664, 30018023, 12951636, 11207636, 31588815, 30863741, 31956453, 33225392, 34078422, 34426522, 24493573, 32441320, 34235359, 26084028, 9398840)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV000840731.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (24)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247536.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

AIRE: PVS1, PM3:Strong, PM2:Supporting, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001978034.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001980556.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005089747.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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