NM_001374828.1(ARID1B):c.4147_4149delinsAG (p.Tyr1383fs) AND Coffin-Siris syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 2, 2022
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:: RCV002470920.2

Allele description [Variation Report for NM_001374828.1(ARID1B):c.4147_4149delinsAG (p.Tyr1383fs)]

NM_001374828.1(ARID1B):c.4147_4149delinsAG (p.Tyr1383fs)

Gene:

ARID1B:AT-rich interaction domain 1B [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

6q25.3

Genomic location:

Preferred name:

NM_001374828.1(ARID1B):c.4147_4149delinsAG (p.Tyr1383fs)

HGVS:

NC_000006.12:g.157190126_157190128delinsAG
NG_066624.1:g.419101_419103delinsAG
NM_001363725.2:c.1648_1650delinsAG
NM_001371656.1:c.4027_4029delinsAG
NM_001374820.1:c.4027_4029delinsAG
NM_001374828.1:c.4147_4149delinsAGMANE SELECT
NM_017519.3:c.3988_3990delinsAG
NM_020732.3:c.3778_3780delTACinsAG
NP_001350654.1:p.Tyr550fs
NP_001358585.1:p.Tyr1343fs
NP_001361749.1:p.Tyr1343fs
NP_001361757.1:p.Tyr1383fs
NP_059989.3:p.Tyr1330fs
NC_000006.11:g.157511260_157511262delinsAG

Protein change:

Y1330fs

Links:

dbSNP: rs1554233122

NCBI 1000 Genomes Browser:

rs1554233122

Molecular consequence:

NM_001363725.2:c.1648_1650delinsAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371656.1:c.4027_4029delinsAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374820.1:c.4027_4029delinsAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374828.1:c.4147_4149delinsAG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017519.3:c.3988_3990delinsAG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Coffin-Siris syndrome 1 (CSS1)
Synonyms:: Mental retardation, autosomal dominant 12
Identifiers:: MONDO: MONDO:0007617; MedGen: C3281201; Orphanet: 1465; OMIM: 135900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002768954	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002768954

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 2, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002768954.1

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

Description

A heterozygous deletion and insertion variant was identified, NM_020732.3(ARID1B):c.3778_3780delinsAG in exon 15 of 20 of the ARID1B gene. This variant is predicted to cause a frameshift from amino acid position 1260 introducing a stop codon 5 residues downstream, NP_065783.3(ARID1B):p.(Tyr1260Serfs*5), resulting in loss of normal protein function through nonsense-mediated decay (NMD). The variant is not present in the gnomAD population database. It has been previously reported in a patient, however no clinical information is available (ClinVar). Other variants predicted to cause NMD have been reported as pathogenic in individuals with Coffin-Siris syndrome (ClinVar, HGMD®). Based on information available at the time of curation, 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 1, 2024

ClinVar

Relating variation to medicine