NM_002016.2(FLG):c.7487del (p.Thr2496fs) AND Ichthyosis vulgaris

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Dec 22, 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:: RCV001782770.6

Allele description [Variation Report for NM_002016.2(FLG):c.7487del (p.Thr2496fs)]

NM_002016.2(FLG):c.7487del (p.Thr2496fs)

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.7487del (p.Thr2496fs)

HGVS:

NC_000001.11:g.152307399del
NG_016190.1:g.22805del
NM_002016.2:c.7487delMANE SELECT
NP_002007.1:p.Thr2496fs
LRG_1028t1:c.7487del
LRG_1028:g.22805del
NC_000001.10:g.152279875del
NM_002016.1:c.7487del
NM_002016.1:c.7487delC

Protein change:

T2496fs

Links:

dbSNP: rs774362740

NCBI 1000 Genomes Browser:

rs774362740

Molecular consequence:

NM_002016.2:c.7487del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV002017788	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002058201	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] PMID:26340974,
SCV004049881	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002017788

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 22, 2023)

germline

clinical testing

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

SCV002058201

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 3, 2022)

germline

clinical testing

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

PMID:26340974,

SCV004049881

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 11, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Revvity Omics, Revvity, SCV002017788.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002058201.1

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

Description

Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_S).The variant has been reported to be associated with FLG related disorder (ClinVar ID: VCV000280218, PMID:26340974, 3billion dataset). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000032, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Genome-Nilou Lab, SCV004049881.1

#	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

Last Updated: Mar 16, 2024

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