NM_006147.4(IRF6):c.174G>A (p.Lys58=) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 25, 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:: RCV001063383.8

Allele description [Variation Report for NM_006147.4(IRF6):c.174G>A (p.Lys58=)]

NM_006147.4(IRF6):c.174G>A (p.Lys58=)

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.174G>A (p.Lys58=)

HGVS:

NC_000001.11:g.209801240C>T
NG_007081.2:g.9895G>A
NM_001206696.2:c.-111-4688G>A
NM_006147.4:c.174G>AMANE SELECT
NP_006138.1:p.Lys58=
NC_000001.10:g.209974585C>T
NM_006147.3:c.174G>A

Links:

dbSNP: rs2077939771

NCBI 1000 Genomes Browser:

rs2077939771

Molecular consequence:

NM_001206696.2:c.-111-4688G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_006147.4:c.174G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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

Recent activity

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Methylorubrum extorquens AM1 plasmid p3META1, complete sequence
Methylorubrum extorquens AM1 plasmid p3META1, complete sequence
gi|240114607|ref|NC_012810.1|

Nucleotide
Achillea millefolium voucher AKM23-488 ribulose-1,5-bisphosphate carboxylase/oxy...
Achillea millefolium voucher AKM23-488 ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast
gi|2612519250|gb|OR670309.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001228225	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 25, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17576681, 9536098, 19282774, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001228225

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 25, 2019)

germline

clinical testing

PubMed (4)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001228225.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with popliteal pterygium syndrome (PMID: 19282774). This sequence change affects codon 58 of the IRF6 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the IRF6 protein. This variant also falls at the last nucleotide of exon 3 of the IRF6 coding sequence, which is part of the consensus splice site for this exon.

#	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: Sep 29, 2024

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