NM_006494.4(ERF):c.1049del (p.Leu350fs) AND Craniosynostosis 4

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 30, 2020
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:: RCV001254631.2

Allele description [Variation Report for NM_006494.4(ERF):c.1049del (p.Leu350fs)]

NM_006494.4(ERF):c.1049del (p.Leu350fs)

Gene:

ERF:ETS2 repressor factor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_006494.4(ERF):c.1049del (p.Leu350fs)

HGVS:

NC_000019.10:g.42249063del
NG_042802.1:g.11102del
NM_001301035.2:c.824del
NM_001308402.2:c.824del
NM_001312656.2:c.824del
NM_006494.4:c.1049delMANE SELECT
NP_001287964.1:p.Leu275fs
NP_001295331.1:p.Leu275fs
NP_001299585.1:p.Leu275fs
NP_006485.2:p.Leu350fs
NC_000019.9:g.42753215del
NM_006494.3:c.1049delT

Protein change:

L275fs

Links:

dbSNP: rs2036390617

NCBI 1000 Genomes Browser:

rs2036390617

Molecular consequence:

NM_001301035.2:c.824del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001308402.2:c.824del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001312656.2:c.824del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006494.4:c.1049del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Craniosynostosis 4
Synonyms:: Lambdoid synostosis; Lambdoidal craniosynostosis
Identifiers:: MONDO: MONDO:0010929; MedGen: C1833340; OMIM: 600775; Human Phenotype Ontology: HP:0004443

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001430658	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 30, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23354439, 26097063, 27738187, 30758909, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001430658

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 30, 2020)

germline

clinical testing

PubMed (5)
[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

Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis.

Twigg SR, Vorgia E, McGowan SJ, Peraki I, Fenwick AL, Sharma VP, Allegra M, Zaragkoulias A, Sadighi Akha E, Knight SJ, Lord H, Lester T, Izatt L, Lampe AK, Mohammed SN, Stewart FJ, Verloes A, Wilson LC, Healy C, Sharpe PT, Hammond P, Hughes J, et al.

Nat Genet. 2013 Mar;45(3):308-13. doi: 10.1038/ng.2539. Epub 2013 Jan 27.

PubMed [citation]

PMID:: 23354439
PMCID:: PMC3683605

Heterozygous mutations in ERF cause syndromic craniosynostosis with multiple suture involvement.

Chaudhry A, Sabatini P, Han L, Ray PN, Forrest C, Bowdin S.

Am J Med Genet A. 2015 Nov;167A(11):2544-7. doi: 10.1002/ajmg.a.37218. Epub 2015 Jun 22.

PubMed [citation]

PMID:: 26097063

See all PubMed Citations (5)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001430658.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This ERF variant is absent in a large population dataset and has not been reported previously in the literature to our knowledge. This frameshift variant is predicted to lead to a premature stop codon in the last exon of the gene, likely escaping nonsense-mediated decay and resulting in a truncated protein product. We consider c.1049delT to be likely 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 15, 2024

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