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NM_000043.6(FAS):c.651+1G>T AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 10, 2018
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:
RCV000805931.6

Allele description [Variation Report for NM_000043.6(FAS):c.651+1G>T]

NM_000043.6(FAS):c.651+1G>T

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.651+1G>T
HGVS:
  • NC_000010.11:g.89012082G>T
  • NG_009089.2:g.26552G>T
  • NM_000043.6:c.651+1G>TMANE SELECT
  • NM_001320619.2:c.569-1261G>T
  • NM_001410956.1:c.696+1G>T
  • NM_152871.4:c.588+1G>T
  • NM_152872.4:c.651+1G>T
  • LRG_134:g.26552G>T
  • NC_000010.10:g.90771839G>T
  • NM_000043.5:c.651+1G>T
Links:
dbSNP: rs1564696849
NCBI 1000 Genomes Browser:
rs1564696849
Molecular consequence:
  • NM_001320619.2:c.569-1261G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000043.6:c.651+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001410956.1:c.696+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_152871.4:c.588+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_152872.4:c.651+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000945906Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Oct 10, 2018)
germlineclinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations.

Siegel RM, Frederiksen JK, Zacharias DA, Chan FK, Johnson M, Lynch D, Tsien RY, Lenardo MJ.

Science. 2000 Jun 30;288(5475):2354-7.

PubMed [citation]
PMID:
10875918
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000945906.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FAS are known to be pathogenic (PMID: 10875918, 22237435). Other variants resulting in disruption of this splice site have been observed in individuals affected with autoimmune lymphoproliferative syndrome (PMID: 15459303, 22237435). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 7 of the FAS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with FAS-related disease.

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

Last Updated: Sep 29, 2024