NM_006147.4(IRF6):c.108_109delinsG (p.Phe36fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 26, 2019
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:: RCV002570373.10

Allele description [Variation Report for NM_006147.4(IRF6):c.108_109delinsG (p.Phe36fs)]

NM_006147.4(IRF6):c.108_109delinsG (p.Phe36fs)

Gene:

IRF6:interferon regulatory factor 6 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1q32.2

Genomic location:

Preferred name:

NM_006147.4(IRF6):c.108_109delinsG (p.Phe36fs)

HGVS:

NC_000001.11:g.209801305_209801306delinsC
NG_007081.2:g.9829_9830delinsG
NM_001206696.2:c.-112+4641_-112+4642delinsG
NM_006147.4:c.108_109delinsGMANE SELECT
NP_006138.1:p.Phe36fs
NC_000001.10:g.209974650_209974651delinsC
NC_000001.10:g.209974650_209974651delinsC
NM_006147.3:c.108_109delinsG

Protein change:

F36fs

Links:

dbSNP: rs2077940243

NCBI 1000 Genomes Browser:

rs2077940243

Molecular consequence:

NM_006147.4:c.108_109delinsG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206696.2:c.-112+4641_-112+4642delinsG - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Orofacial cleft 6, susceptibility to (OFC6)
Synonyms:: CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 6
Identifiers:: MONDO: MONDO:0012141; MedGen: C1837213; OMIM: 608864

Name:: Popliteal pterygium syndrome (PPS)
Identifiers:: MONDO: MONDO:0017435; MedGen: C0265259

Name:: Van der Woude syndrome
Synonyms:: Lip pit syndrome
Identifiers:: MONDO: MONDO:0019508; MedGen: C0175697; Orphanet: 888

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421736	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19282774, 23949966, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001421736

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2019)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome.

de Lima RL, Hoper SA, Ghassibe M, Cooper ME, Rorick NK, Kondo S, Katz L, Marazita ML, Compton J, Bale S, Hehr U, Dixon MJ, Daack-Hirsch S, Boute O, Bayet B, Revencu N, Verellen-Dumoulin C, Vikkula M, Richieri-Costa A, Moretti-Ferreira D, Murray JC, Schutte BC.

Genet Med. 2009 Apr;11(4):241-7. doi: 10.1097/GIM.0b013e318197a49a.

PubMed [citation]

PMID:: 19282774
PMCID:: PMC2789395

Search for genetic modifiers of IRF6 and genotype-phenotype correlations in Van der Woude and popliteal pterygium syndromes.

Leslie EJ, Mancuso JL, Schutte BC, Cooper ME, Durda KM, L'Heureux J, Zucchero TM, Marazita ML, Murray JC.

Am J Med Genet A. 2013 Oct;161A(10):2535-2544. doi: 10.1002/ajmg.a.36133. Epub 2013 Aug 15.

PubMed [citation]

PMID:: 23949966
PMCID:: PMC3898350

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001421736.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in IRF6 are known to be pathogenic (PMID: 19282774, 23949966). This variant has not been reported in the literature in individuals with IRF6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe36Leufs*27) in the IRF6 gene. It is expected to result in an absent or disrupted protein product.

#	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

Last Updated: Oct 26, 2024

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