NM_207361.6(FREM2):c.2206C>T (p.Arg736Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 14, 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:: RCV001702715.4

Allele description [Variation Report for NM_207361.6(FREM2):c.2206C>T (p.Arg736Ter)]

NM_207361.6(FREM2):c.2206C>T (p.Arg736Ter)

Gene:

FREM2:FRAS1 related extracellular matrix 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.3

Genomic location:

Preferred name:

NM_207361.6(FREM2):c.2206C>T (p.Arg736Ter)

HGVS:

NC_000013.11:g.38689550C>T
NG_008125.2:g.7515C>T
NM_207361.6:c.2206C>TMANE SELECT
NP_997244.4:p.Arg736Ter
NC_000013.10:g.39263687C>T
NM_207361.5:c.2206C>T

Protein change:

R736*; ARG736TER

Links:

OMIM: 608945.0006; dbSNP: rs939534674

NCBI 1000 Genomes Browser:

rs939534674

Molecular consequence:

NM_207361.6:c.2206C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001928261	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001974942	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV004509492	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18203166, 26552811, 30802441, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001928261

Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV001974942

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV004509492

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Fraser syndrome due to homozygosity for a splice site mutation of FREM2.

Shafeghati Y, Kniepert A, Vakili G, Zenker M.

Am J Med Genet A. 2008 Feb 15;146A(4):529-31. doi: 10.1002/ajmg.a.32091. No abstract available.

PubMed [citation]

PMID:: 18203166

Prenatal diagnosis of Fraser syndrome: a matter of life or death?

De Bernardo G, Giordano M, Di Toro A, Sordino D, De Brasi D.

Ital J Pediatr. 2015 Nov 9;41:86. doi: 10.1186/s13052-015-0195-6.

PubMed [citation]

PMID:: 26552811
PMCID:: PMC4640198

See all PubMed Citations (4)

Details of each submission

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001928261.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001974942.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004509492.1

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

Description

This sequence change creates a premature translational stop signal (p.Arg736*) in the FREM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FREM2 are known to be pathogenic (PMID: 18203166, 26552811). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of Fraser syndrome (PMID: 30802441). ClinVar contains an entry for this variant (Variation ID: 625182). 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: Sep 29, 2024

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