NM_000043.6(FAS):c.617del (p.Asn206fs) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 4, 2019
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:: RCV001050531.7

Allele description [Variation Report for NM_000043.6(FAS):c.617del (p.Asn206fs)]

NM_000043.6(FAS):c.617del (p.Asn206fs)

Gene:

FAS:Fas cell surface death receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_000043.6(FAS):c.617del (p.Asn206fs)

HGVS:

NC_000010.11:g.89012047del
NG_009089.2:g.26517del
NM_000043.6:c.617delMANE SELECT
NM_001320619.2:c.568+1232del
NM_152871.4:c.554del
NM_152872.4:c.617del
NP_000034.1:p.Asn206fs
NP_690610.1:p.Asn185fs
NP_690611.1:p.Asn206fs
LRG_134:g.26517del
NC_000010.10:g.90771801del
NC_000010.10:g.90771804del
NM_000043.5:c.617del
NR_028033.4:n.524del
NR_028034.4:n.386del
NR_028035.4:n.449del
NR_028036.4:n.587del
NR_135314.2:n.783del
NR_135315.2:n.536del

Protein change:

N185fs

Links:

dbSNP: rs1848558128

NCBI 1000 Genomes Browser:

rs1848558128

Molecular consequence:

NM_000043.6:c.617del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152871.4:c.554del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152872.4:c.617del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001320619.2:c.568+1232del - intron variant - [Sequence Ontology: SO:0001627]
NR_028033.4:n.524del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028034.4:n.386del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028035.4:n.449del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028036.4:n.587del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135314.2:n.783del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135315.2:n.536del - 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
SCV001214646	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 4, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10090885, 21490157, 23407489, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214646

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 4, 2019)

germline

clinical testing

PubMed (4)
[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

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

FAS haploinsufficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome.

Kuehn HS, Caminha I, Niemela JE, Rao VK, Davis J, Fleisher TA, Oliveira JB.

J Immunol. 2011 May 15;186(10):6035-43. doi: 10.4049/jimmunol.1100021. Epub 2011 Apr 13.

PubMed [citation]

PMID:: 21490157
PMCID:: PMC3725553

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001214646.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. 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, 21490157, 23407489). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with FAS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the FAS gene (p.Asn206Thrfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 130 amino acids of the FAS protein.

#	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: Feb 28, 2024

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