U.S. flag

An official website of the United States government

NM_000043.6(FAS):c.814G>A (p.Glu272Lys) AND Autoimmune lymphoproliferative syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 21, 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:
RCV003037352.3

Allele description [Variation Report for NM_000043.6(FAS):c.814G>A (p.Glu272Lys)]

NM_000043.6(FAS):c.814G>A (p.Glu272Lys)

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.814G>A (p.Glu272Lys)
HGVS:
  • NC_000010.11:g.89014256G>A
  • NG_009089.2:g.28726G>A
  • NM_000043.6:c.814G>AMANE SELECT
  • NM_001320619.2:c.*137G>A
  • NM_001410956.1:c.859G>A
  • NM_152871.4:c.751G>A
  • NM_152872.4:c.*126G>A
  • NP_000034.1:p.Glu272Lys
  • NP_000034.1:p.Glu272Lys
  • NP_001397885.1:p.Glu287Lys
  • NP_690610.1:p.Glu251Lys
  • LRG_134t1:c.814G>A
  • LRG_134:g.28726G>A
  • LRG_134p1:p.Glu272Lys
  • NC_000010.10:g.90774013G>A
  • NM_000043.4:c.814G>A
  • NR_028033.4:n.721G>A
  • NR_028034.4:n.583G>A
  • NR_028035.4:n.646G>A
  • NR_028036.4:n.784G>A
  • NR_135313.2:n.701G>A
  • NR_135314.2:n.980G>A
  • NR_135315.2:n.733G>A
Protein change:
E251K
Molecular consequence:
  • NM_001320619.2:c.*137G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_152872.4:c.*126G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000043.6:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410956.1:c.859G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152871.4:c.751G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_028033.4:n.721G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028034.4:n.583G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028035.4:n.646G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_028036.4:n.784G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_135313.2:n.701G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_135314.2:n.980G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_135315.2:n.733G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003439553Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 21, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations.

Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H.

Nat Struct Mol Biol. 2010 Nov;17(11):1324-9. doi: 10.1038/nsmb.1920. Epub 2010 Oct 10.

PubMed [citation]
PMID:
20935634
PMCID:
PMC2988912

Lymphoproliferative syndrome with autoimmunity: A possible genetic basis for dominant expression of the clinical manifestations.

Rieux-Laucat F, Blachère S, Danielan S, De Villartay JP, Oleastro M, Solary E, Bader-Meunier B, Arkwright P, Pondaré C, Bernaudin F, Chapel H, Nielsen S, Berrah M, Fischer A, Le Deist F.

Blood. 1999 Oct 15;94(8):2575-82.

PubMed [citation]
PMID:
10515860
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439553.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FAS function (PMID: 20935634). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FAS protein function. This variant is also known as E256K. This missense change has been observed in individual(s) with autosomal dominant autoimmune lymphoproliferative syndrome (PMID: 10515860; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 272 of the FAS protein (p.Glu272Lys).

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

Last Updated: Sep 29, 2024