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NM_000268.4(NF2):c.12_22delinsTTCA (p.Ile5fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 3, 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:
RCV003297520.2

Allele description [Variation Report for NM_000268.4(NF2):c.12_22delinsTTCA (p.Ile5fs)]

NM_000268.4(NF2):c.12_22delinsTTCA (p.Ile5fs)

Gene:
NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.12_22delinsTTCA (p.Ile5fs)
HGVS:
  • NC_000022.11:g.29604010_29604020delinsTTCA
  • NG_009057.1:g.5455_5465delinsTTCA
  • NG_201599.1:g.712_722delinsTTCA
  • NM_000268.4:c.12_22delinsTTCAMANE SELECT
  • NM_001407053.1:c.-219_-209delinsTTCA
  • NM_001407054.1:c.12_22delinsTTCA
  • NM_001407055.1:c.12_22delinsTTCA
  • NM_001407056.1:c.-219_-209delinsTTCA
  • NM_001407057.1:c.12_22delinsTTCA
  • NM_001407058.1:c.12_22delinsTTCA
  • NM_001407059.1:c.12_22delinsTTCA
  • NM_001407060.1:c.12_22delinsTTCA
  • NM_001407062.1:c.12_22delinsTTCA
  • NM_001407063.1:c.12_22delinsTTCA
  • NM_001407064.1:c.12_22delinsTTCA
  • NM_001407065.1:c.-629_-619delinsTTCA
  • NM_001407066.1:c.12_22delinsTTCA
  • NM_001407067.1:c.-245_-235delinsTTCA
  • NM_016418.5:c.12_22delinsTTCA
  • NM_181825.3:c.12_22delinsTTCA
  • NM_181828.3:c.12_22delinsTTCA
  • NM_181829.3:c.12_22delinsTTCA
  • NM_181830.3:c.12_22delinsTTCA
  • NM_181831.3:c.12_22delinsTTCA
  • NM_181832.3:c.12_22delinsTTCA
  • NM_181833.3:c.12_22delinsTTCA
  • NP_000259.1:p.Ile5Serfs
  • NP_000259.1:p.Ile5fs
  • NP_001393983.1:p.Ile5fs
  • NP_001393984.1:p.Ile5fs
  • NP_001393986.1:p.Ile5fs
  • NP_001393987.1:p.Ile5fs
  • NP_001393988.1:p.Ile5fs
  • NP_001393989.1:p.Ile5fs
  • NP_001393991.1:p.Ile5fs
  • NP_001393992.1:p.Ile5fs
  • NP_001393993.1:p.Ile5fs
  • NP_001393995.1:p.Ile5fs
  • NP_057502.2:p.Ile5fs
  • NP_861546.1:p.Ile5fs
  • NP_861966.1:p.Ile5fs
  • NP_861967.1:p.Ile5fs
  • NP_861968.1:p.Ile5fs
  • NP_861969.1:p.Ile5fs
  • NP_861970.1:p.Ile5fs
  • NP_861971.1:p.Ile5fs
  • LRG_511t1:c.12_22delCATCGCTTCCCinsTTCA
  • LRG_511t2:c.12_22delinsTTCA
  • LRG_511:g.5455_5465delinsTTCA
  • LRG_511p1:p.Ile5Serfs
  • LRG_511p2:p.Ile5fs
  • NC_000022.10:g.29999999_30000009delinsTTCA
  • NM_000268.3:c.12_22del11insTTCA
  • NM_000268.3:c.12_22delCATCGCTTCCCinsTTCA
  • NR_156186.2:n.378_388delCATCGCTTCCCinsTTCA
  • NR_176267.1:n.378_388delinsTTCA
Protein change:
I5fs
Molecular consequence:
  • NM_001407053.1:c.-219_-209delinsTTCA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407056.1:c.-219_-209delinsTTCA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407065.1:c.-629_-619delinsTTCA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407067.1:c.-245_-235delinsTTCA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000268.4:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407054.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407055.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407057.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407058.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407059.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407060.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407062.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407063.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407064.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407066.1:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_016418.5:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181825.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181828.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181829.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181830.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181831.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181832.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_181833.3:c.12_22delinsTTCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_176267.1:n.378_388delinsTTCA - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004007046Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(May 3, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV004007046.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.12_22del11insTTCA variant, located in coding exon 1 of the NF2 gene, results from the deletion of 11 nucleotides and insertion of 4 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.I5Sfs*3). The predicted stop codon occurs in the 5’ end of NF2 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024