NM_000043.6(FAS):c.869C>A (p.Ala290Glu) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2022
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:: RCV001347118.7

Allele description [Variation Report for NM_000043.6(FAS):c.869C>A (p.Ala290Glu)]

NM_000043.6(FAS):c.869C>A (p.Ala290Glu)

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.869C>A (p.Ala290Glu)

HGVS:

NC_000010.11:g.89014311C>A
NG_009089.2:g.28781C>A
NM_000043.6:c.869C>AMANE SELECT
NM_001320619.2:c.*192C>A
NM_152871.4:c.806C>A
NM_152872.4:c.*181C>A
NP_000034.1:p.Ala290Glu
NP_690610.1:p.Ala269Glu
LRG_134:g.28781C>A
NC_000010.10:g.90774068C>A
NR_028033.4:n.776C>A
NR_028034.4:n.638C>A
NR_028035.4:n.701C>A
NR_028036.4:n.839C>A
NR_135313.2:n.756C>A
NR_135314.2:n.1035C>A
NR_135315.2:n.788C>A

Protein change:

A269E

Links:

dbSNP: rs760993872

NCBI 1000 Genomes Browser:

rs760993872

Molecular consequence:

NM_001320619.2:c.*192C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152872.4:c.*181C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000043.6:c.869C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_152871.4:c.806C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_028033.4:n.776C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028034.4:n.638C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028035.4:n.701C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028036.4:n.839C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135313.2:n.756C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135314.2:n.1035C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135315.2:n.788C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001541363	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22983577, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001541363

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults.

Lambotte O, Neven B, Galicier L, Magerus-Chatinet A, Schleinitz N, Hermine O, Meyts I, Picard C, Godeau B, Fischer A, Rieux-Laucat F.

Haematologica. 2013 Mar;98(3):389-92. doi: 10.3324/haematol.2012.067488. Epub 2012 Sep 14.

PubMed [citation]

PMID:: 22983577
PMCID:: PMC3659930

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001541363.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1043064). This missense change has been observed in individual(s) with autoimmune lymphoproliferative syndrome (PMID: 22983577). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 290 of the FAS protein (p.Ala290Glu).

#	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: Sep 29, 2024

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