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NM_000043.6(FAS):c.644T>A (p.Leu215Ter) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 7, 2020
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:
RCV001383519.7

Allele description [Variation Report for NM_000043.6(FAS):c.644T>A (p.Leu215Ter)]

NM_000043.6(FAS):c.644T>A (p.Leu215Ter)

Gene:
FAS:Fas cell surface death receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_000043.6(FAS):c.644T>A (p.Leu215Ter)
HGVS:
  • NC_000010.11:g.89012074T>A
  • NG_009089.2:g.26544T>A
  • NM_000043.6:c.644T>AMANE SELECT
  • NM_001320619.2:c.568+1259T>A
  • NM_152871.4:c.581T>A
  • NM_152872.4:c.644T>A
  • NP_000034.1:p.Leu215Ter
  • NP_690610.1:p.Leu194Ter
  • NP_690611.1:p.Leu215Ter
  • LRG_134:g.26544T>A
  • NC_000010.10:g.90771831T>A
  • NR_028033.4:n.551T>A
  • NR_028034.4:n.413T>A
  • NR_028035.4:n.476T>A
  • NR_028036.4:n.614T>A
  • NR_135314.2:n.810T>A
  • NR_135315.2:n.563T>A
Protein change:
L194*
Links:
dbSNP: rs2133539468
NCBI 1000 Genomes Browser:
rs2133539468
Molecular consequence:
  • NM_001320619.2:c.568+1259T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NR_028033.4:n.551T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028034.4:n.413T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028035.4:n.476T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028036.4:n.614T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_135314.2:n.810T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_135315.2:n.563T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000043.6:c.644T>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_152871.4:c.581T>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_152872.4:c.644T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Autoimmune lymphoproliferative syndrome type 1 (ALPS)
Synonyms:
Autoimmune lymphoproliferative syndrome type 1, autosomal dominant; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE I, AUTOSOMAL DOMINANT
Identifiers:
MONDO: MONDO:0011158; MedGen: C1328840; Orphanet: 3261; OMIM: 601859

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001582670Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 7, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance.

Jackson CE, Fischer RE, Hsu AP, Anderson SM, Choi Y, Wang J, Dale JK, Fleisher TA, Middelton LA, Sneller MC, Lenardo MJ, Straus SE, Puck JM.

Am J Hum Genet. 1999 Apr;64(4):1002-14.

PubMed [citation]
PMID:
10090885
PMCID:
PMC1377824

Autoimmune pancreatitis in the autoimmune lymphoproliferative syndrome (ALPS): a sheep in wolves' clothing?

Langan RC, Gill F, Raiji MT, Mullinax JE, Pittaluga S, Pandalai P, Davis J, Perkins K, Avital I, Rudloff U.

Pancreas. 2013 Mar;42(2):363-6. doi: 10.1097/MPA.0b013e3182648778. No abstract available.

PubMed [citation]
PMID:
23407489
PMCID:
PMC3573327
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582670.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change results in a premature translational stop signal in the FAS gene (p.Leu215*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 121 amino acids of the FAS protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FAS-related conditions. This variant disrupts the C-terminus of the FAS protein. Other variant(s) that disrupt this region (p.Leu294*) have been determined to be pathogenic (PMID: 10090885, 23407489, 2149015). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Sep 29, 2024