NM_006147.4(IRF6):c.1234C>T (p.Arg412Ter) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 26, 2023
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:: RCV000684776.7

Allele description

NM_006147.4(IRF6):c.1234C>T (p.Arg412Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.2

Genomic location:

Preferred name:

NM_006147.4(IRF6):c.1234C>T (p.Arg412Ter)

HGVS:

NC_000001.11:g.209788590G>A
NG_007081.2:g.22545C>T
NM_001206696.2:c.949C>T
NM_006147.4:c.1234C>TMANE SELECT
NP_001193625.1:p.Arg317Ter
NP_006138.1:p.Arg412Ter
NC_000001.10:g.209961935G>A
NM_006147.3:c.1234C>T

Protein change:

R317*

Links:

dbSNP: rs1553247595

NCBI 1000 Genomes Browser:

rs1553247595

Molecular consequence:

NM_001206696.2:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_006147.4:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Mus musculus cDNA clone IMAGE:4188600, containing frame-shift errors
Mus musculus cDNA clone IMAGE:4188600, containing frame-shift errors
gi|15126663|gb|BC012260.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630083	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12219090, 19282774, 19623037, 21468557, 23154523, 25784454, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630083

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2023)

germline

clinical testing

PubMed (7)
[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

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, et al.

Nat Genet. 2002 Oct;32(2):285-9. Epub 2002 Sep 3.

PubMed [citation]

PMID:: 12219090
PMCID:: PMC3169431

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

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000630083.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg412*) in the IRF6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acid(s) of the IRF6 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Van der Woude syndrome and popliteal pterygium syndrome (PMID: 12219090, 19282774, 19623037, 21468557, 23154523). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 458682). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects IRF6 function (PMID: 25784454). For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 6, 2024

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