NM_005862.3(STAG1):c.3241C>T (p.Arg1081Ter) AND Intellectual disability, autosomal dominant 47

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 28, 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:: RCV003493272.1

Allele description [Variation Report for NM_005862.3(STAG1):c.3241C>T (p.Arg1081Ter)]

NM_005862.3(STAG1):c.3241C>T (p.Arg1081Ter)

Gene:

STAG1:STAG1 cohesin complex component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q22.3

Genomic location:

Preferred name:

NM_005862.3(STAG1):c.3241C>T (p.Arg1081Ter)

HGVS:

NC_000003.12:g.136349188G>A
NM_005862.3:c.3241C>TMANE SELECT
NP_005853.2:p.Arg1081Ter
NC_000003.11:g.136068030G>A

Protein change:

R1081*

Molecular consequence:

NM_005862.3:c.3241C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Intellectual disability, autosomal dominant 47
Synonyms:: MENTAL RETARDATION, AUTOSOMAL DOMINANT 47; INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 47
Identifiers:: MONDO: MONDO:0030912; MedGen: C4539951; OMIM: 617635

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004239023	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28119487, 30158690, 34440290, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004239023

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 28, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability.

Lehalle D, Mosca-Boidron AL, Begtrup A, Boute-Benejean O, Charles P, Cho MT, Clarkson A, Devinsky O, Duffourd Y, Duplomb-Jego L, Gérard B, Jacquette A, Kuentz P, Masurel-Paulet A, McDougall C, Moutton S, Olivié H, Park SM, Rauch A, Revencu N, Rivière JB, Rubin K, et al.

J Med Genet. 2017 Jul;54(7):479-488. doi: 10.1136/jmedgenet-2016-104468. Epub 2017 Jan 24.

PubMed [citation]

PMID:: 28119487

Clinical exome sequencing reveals locus heterogeneity and phenotypic variability of cohesinopathies.

Yuan B, Neira J, Pehlivan D, Santiago-Sim T, Song X, Rosenfeld J, Posey JE, Patel V, Jin W, Adam MP, Baple EL, Dean J, Fong CT, Hickey SE, Hudgins L, Leon E, Madan-Khetarpal S, Rawlins L, Rustad CF, Stray-Pedersen A, Tveten K, Wenger O, et al.

Genet Med. 2019 Mar;21(3):663-675. doi: 10.1038/s41436-018-0085-6. Epub 2018 Aug 30.

PubMed [citation]

PMID:: 30158690
PMCID:: PMC6395558

See all PubMed Citations (4)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV004239023.1

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

Description

This STAG1 variant is absent from a large population dataset and has not been reported in ClinVar nor the literature, to our knowledge. This nonsense variant results in a premature stop codon in exon 29 of 34 likely leading to nonsense-mediated decay and lack of protein production. Bioinformatic analysis predicts that this variant would not affect normal exon 29 splicing, although this has not been confirmed experimentally to our knowledge. We consider this variant to be likely pathogenic for autosomal dominant intellectual developmental disorder-47.

#	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: Feb 14, 2024

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