NM_005612.5(REST):c.177_181del (p.Asn59fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2024
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:: RCV003552207.2

Allele description [Variation Report for NM_005612.5(REST):c.177_181del (p.Asn59fs)]

NM_005612.5(REST):c.177_181del (p.Asn59fs)

Gene:

REST:RE1 silencing transcription factor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_005612.5(REST):c.177_181del (p.Asn59fs)

HGVS:

NC_000004.12:g.56910815_56910819del
NG_029447.1:g.7940_7944del
NM_001193508.1:c.177_181del
NM_001363453.2:c.177_181del
NM_005612.5:c.177_181delMANE SELECT
NP_001180437.1:p.Asn59fs
NP_001350382.1:p.Asn59fs
NP_005603.3:p.Asn59fs
NC_000004.11:g.57776980_57776984del
NC_000004.11:g.57776981_57776985del

Protein change:

N59fs

Molecular consequence:

NM_001193508.1:c.177_181del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363453.2:c.177_181del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005612.5:c.177_181del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004262996	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 1, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26551668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004262996

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 1, 2024)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the transcriptional repressor REST predispose to Wilms tumor.

Mahamdallie SS, Hanks S, Karlin KL, Zachariou A, Perdeaux ER, Ruark E, Shaw CA, Renwick A, Ramsay E, Yost S, Elliott A, Birch J, Capra M, Gray J, Hale J, Kingston J, Levitt G, McLean T, Sheridan E, Renwick A, Seal S, Stiller C, et al.

Nat Genet. 2015 Dec;47(12):1471-4. doi: 10.1038/ng.3440. Epub 2015 Nov 9. Erratum in: Nat Genet. 2016 Apr;48(4):473. doi: 10.1038/ng0329-473d.

PubMed [citation]

PMID:: 26551668

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004262996.1

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

Description

This sequence change creates a premature translational stop signal (p.Asn59Lysfs*4) in the REST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in REST are known to be pathogenic (PMID: 26551668). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with REST-related conditions. 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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