NM_000043.6(FAS):c.879_880del (p.Leu294fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 7, 2016
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:: RCV000255803.1

Allele description [Variation Report for NM_000043.6(FAS):c.879_880del (p.Leu294fs)]

NM_000043.6(FAS):c.879_880del (p.Leu294fs)

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.879_880del (p.Leu294fs)

HGVS:

NC_000010.11:g.89014321_89014322del
NG_009089.2:g.28791_28792del
NM_000043.6:c.879_880delMANE SELECT
NM_001320619.2:c.*202_*203del
NM_152871.4:c.816_817del
NM_152872.4:c.*191_*192del
NP_000034.1:p.Leu294fs
NP_690610.1:p.Leu273fs
LRG_134t1:c.879_880del
LRG_134:g.28791_28792del
NC_000010.10:g.90774078_90774079del
NM_000043.4:c.879_880delAT
NR_028033.4:n.786_787del
NR_028034.4:n.648_649del
NR_028035.4:n.711_712del
NR_028036.4:n.849_850del
NR_135313.2:n.766_767del
NR_135314.2:n.1045_1046del
NR_135315.2:n.798_799del

Protein change:

L273fs

Links:

dbSNP: rs886039524

NCBI 1000 Genomes Browser:

rs886039524

Molecular consequence:

NM_001320619.2:c.*202_*203del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152872.4:c.*191_*192del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000043.6:c.879_880del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152871.4:c.816_817del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_028033.4:n.786_787del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028034.4:n.648_649del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028035.4:n.711_712del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_028036.4:n.849_850del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135313.2:n.766_767del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135314.2:n.1045_1046del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_135315.2:n.798_799del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000322259	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 7, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000322259

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 7, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000322259.7

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

Description

The c.879_880delAT pathogenic variant in the FAS gene has been reported previously in association with autoimmune lymphoproliferative syndrome (ALPS) type 1A (Lo et al., 2013; Kuehn et al., 2011). The deletion causes a frameshift starting with codon Leucine 294, changes this amino acid to an Aspartic acid residue and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Leu294AspfsX2. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation. Functional studies have shown that c.879_880delAT results in increased FAS surface expression and impaired apoptosis (Kuehn et al., 2011). Additionally, the variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.

#	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

Last Updated: Feb 20, 2024

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