NM_001378974.1(FBXW11):c.1154C>A (p.Ala385Asp) AND Neurodevelopmental, jaw, eye, and digital syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 13, 2021
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:: RCV001175173.3

Allele description [Variation Report for NM_001378974.1(FBXW11):c.1154C>A (p.Ala385Asp)]

NM_001378974.1(FBXW11):c.1154C>A (p.Ala385Asp)

Gene:

FBXW11:F-box and WD repeat domain containing 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.1

Genomic location:

Preferred name:

NM_001378974.1(FBXW11):c.1154C>A (p.Ala385Asp)

HGVS:

NC_000005.10:g.171876352G>T
NG_009275.1:g.135522C>A
NG_009275.2:g.135522C>A
NM_001378974.1:c.1154C>AMANE SELECT
NM_001378975.1:c.1085C>A
NM_001378976.1:c.1058C>A
NM_001378977.1:c.995C>A
NM_001378978.1:c.995C>A
NM_001378979.1:c.995C>A
NM_001378980.1:c.989C>A
NM_012300.3:c.1091C>A
NM_033644.3:c.1052C>A
NM_033645.3:c.989C>A
NP_001365903.1:p.Ala385Asp
NP_001365904.1:p.Ala362Asp
NP_001365905.1:p.Ala353Asp
NP_001365906.1:p.Ala332Asp
NP_001365907.1:p.Ala332Asp
NP_001365908.1:p.Ala332Asp
NP_001365909.1:p.Ala330Asp
NP_036432.2:p.Ala364Asp
NP_387448.2:p.Ala351Asp
NP_387449.2:p.Ala330Asp
NC_000005.9:g.171303356G>T
NM_012300.2:c.1091C>A

Protein change:

A330D; ALA364ASP

Links:

OMIM: 605651.0002; dbSNP: rs1758081491

NCBI 1000 Genomes Browser:

rs1758081491

Molecular consequence:

NM_001378974.1:c.1154C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378975.1:c.1085C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378976.1:c.1058C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378977.1:c.995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378978.1:c.995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378979.1:c.995C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378980.1:c.989C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012300.3:c.1091C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033644.3:c.1052C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033645.3:c.989C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neurodevelopmental, jaw, eye, and digital syndrome (NEDJED)
Identifiers:: MONDO: MONDO:0030057; MedGen: C5394477; OMIM: 618914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001338772	OMIM	no assertion criteria provided	Pathogenic (Jun 16, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001571398	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 13, 2021)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 31402090, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001338772

OMIM

no assertion criteria provided

Pathogenic
(Jun 16, 2020)

germline

literature only

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

SCV001571398

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 13, 2021)

unknown

curation

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

De Novo Missense Variants in FBXW11 Cause Diverse Developmental Phenotypes Including Brain, Eye, and Digit Anomalies.

Holt RJ, Young RM, Crespo B, Ceroni F, Curry CJ, Bellacchio E, Bax DA, Ciolfi A, Simon M, Fagerberg CR, van Binsbergen E, De Luca A, Memo L, Dobyns WB, Mohammed AA, Clokie SJH, Zazo Seco C, Jiang YH, Sørensen KP, Andersen H, Sullivan J, Powis Z, et al.

Am J Hum Genet. 2019 Sep 5;105(3):640-657. doi: 10.1016/j.ajhg.2019.07.005. Epub 2019 Aug 8.

PubMed [citation]

PMID:: 31402090
PMCID:: PMC6731360

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, SCV001338772.1

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

Description

In a 9-year-old boy (individual 2) with neurodevelopmental, jaw, eye, and digital syndrome (NEDJED; 618914), Holt et al. (2019) identified heterozygosity for a de novo c.1091C-A transversion (c.1091C-A, NM_012300.2) in exon 13 of the FBXW11 gene, resulting in an ala364-to-asp (A364D) substitution at a highly conserved residue at the N-terminal end of the WD4 repeat within the WD40 domain. The mutation was not found in the gnomAD database.

#	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 SIB Swiss Institute of Bioinformatics, SCV001571398.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

This variant is interpreted as likely pathogenic for Neurodevelopmental, jaw, eye, and digital syndrome, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Assumed de novo, but no confirmation of paternity and maternity (PM6); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2).

#	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: Apr 23, 2022

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