U.S. flag

An official website of the United States government

NM_002016.2(FLG):c.2476C>T (p.Arg826Ter) AND FLG-related disorder

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 5, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV003401213.7

Allele description [Variation Report for NM_002016.2(FLG):c.2476C>T (p.Arg826Ter)]

NM_002016.2(FLG):c.2476C>T (p.Arg826Ter)

Genes:
CCDST:cervical cancer associated DHX9 suppressive transcript [Gene - HGNC]
FLG:filaggrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q21.3
Genomic location:
Preferred name:
NM_002016.2(FLG):c.2476C>T (p.Arg826Ter)
HGVS:
  • NC_000001.11:g.152312410G>A
  • NG_016190.1:g.17794C>T
  • NM_002016.2:c.2476C>TMANE SELECT
  • NP_002007.1:p.Arg826Ter
  • NP_002007.1:p.Arg826Ter
  • LRG_1028t1:c.2476C>T
  • LRG_1028:g.17794C>T
  • LRG_1028p1:p.Arg826Ter
  • NC_000001.10:g.152284886G>A
  • NM_002016.1:c.2476C>T
  • p.R826*
Protein change:
R826*
Links:
dbSNP: rs115746363
NCBI 1000 Genomes Browser:
rs115746363
Molecular consequence:
  • NM_002016.2:c.2476C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
FLG-related disorder
Synonyms:
FLG-related condition; FLG-related disorders
Identifiers:

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
SCV001451539Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)		Pathogenic
(Sep 5, 2024) 		unknownclinical testing

Citation Link,

SCV004111815PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 24, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001451539.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From PreventionGenetics, part of Exact Sciences, SCV004111815.1

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

Description

The FLG c.2476C>T variant is predicted to result in premature protein termination (p.Arg826*). This variant has been reported in the heterozygous state in multiple individuals affected by atopic dermatitis, ichthyosis vulgaris, and psoriasis vulgaris, including a control individual later discovered to have a history of asthma (Table 2, Zhang et al. 2010. PubMed ID: 21039602; Table 2, Hu et al. 2012. PubMed ID: 22407025; Table 1, Polcari et al. 2014. PubMed ID: 24920311; Table 1, Mathyer et al. 2018. PubMed ID: 29791750; Table 1, Margolis et al. 2019. PubMed ID: 31365035). This variant is reported in 0.76% of alleles in individuals of African descent, including two homozygotes, in gnomAD (http://gnomad.broadinstitute.org/variant/1-152284886-G-A). Variable expressivity and differing environmental factors may help explain the presence of this loss-of-function FLG variant in individuals in the general population. Nonsense variants in FLG are expected to be pathogenic. This variant is interpreted as pathogenic.

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

Last Updated: Nov 3, 2024