NM_002016.2(FLG):c.3321del (p.Gly1109fs) AND Ichthyosis vulgaris

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Dec 25, 2023
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:: RCV000017718.34

Allele description [Variation Report for NM_002016.2(FLG):c.3321del (p.Gly1109fs)]

NM_002016.2(FLG):c.3321del (p.Gly1109fs)

Genes:

CCDST:cervical cancer associated DHX9 suppressive transcript [Gene - HGNC]
FLG:filaggrin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_002016.2(FLG):c.3321del (p.Gly1109fs)

HGVS:

NC_000001.11:g.152311565del
NG_016190.1:g.18639del
NM_002016.2:c.3321delMANE SELECT
NP_002007.1:p.Gly1109fs
LRG_1028t1:c.3321del
LRG_1028:g.18639del
NC_000001.10:g.152284041del
NC_000001.11:g.152311565_152311565delT
NM_002016.1:c.3321del
NM_002016.1:c.3321delA

Protein change:

G1109fs

Links:

OMIM: 135940.0004; dbSNP: rs200519781

NCBI 1000 Genomes Browser:

rs200519781

Molecular consequence:

NM_002016.2:c.3321del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Ichthyosis vulgaris
Synonyms:: Ichthyosis simplex; Dominant ichthyosis vulgaris
Identifiers:: MONDO: MONDO:0024304; MedGen: C0079584; OMIM: 146700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037995	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2007)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001142308	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Pathogenic (Jan 6, 2020)	germline	curation
SCV002516391	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link,
SCV004050257	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005049880	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 25, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis.

Nomura T, Sandilands A, Akiyama M, Liao H, Evans AT, Sakai K, Ota M, Sugiura H, Yamamoto K, Sato H, Palmer CN, Smith FJ, McLean WH, Shimizu H.

J Allergy Clin Immunol. 2007 Feb;119(2):434-40.

PubMed [citation]

PMID:: 17291859

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 OMIM, SCV000037995.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 probands from 2 unrelated Japanese families with ichthyosis vulgaris (146700), who were negative for previously identified null mutations in the FLG gene, Nomura et al. (2007) identified heterozygosity for a 1-bp deletion (3321delA) in exon 3 of the FLG gene, resulting in a premature termination of profilaggrin translation in filaggrin repeat domain 2. The authors then screened 143 Japanese patients with atopic dermatitis (605803) from 140 unrelated families for this deletion and identified 3321delA in 2 patients. The deletion was not found in 156 unrelated nonatopic and nonichthyotic Japanese controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Reproductive Health Research and Development, BGI Genomics, SCV001142308.1

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

Description

NM_002016.1:c.3321delA in the FLG gene has an allele frequency of 0.01 in East Asia subpopulation in the gnomAD database.This variant is predicted to cause loss of normal protein function through protein truncation. The patient's phenotype is highly specific for FLG (PMID: 17291859). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PVS1; PM2_supporting; PP4.

#	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

From Mendelics, SCV002516391.1

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

#	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

From Genome-Nilou Lab, SCV004050257.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV005049880.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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