NM_001374828.1(ARID1B):c.4488del (p.Lys1496fs) AND Coffin-Siris syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 2, 2020
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:: RCV002471483.1

Allele description [Variation Report for NM_001374828.1(ARID1B):c.4488del (p.Lys1496fs)]

NM_001374828.1(ARID1B):c.4488del (p.Lys1496fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

6q25.3

Genomic location:

Preferred name:

NM_001374828.1(ARID1B):c.4488del (p.Lys1496fs)

HGVS:

NC_000006.12:g.157200713del
NG_066624.1:g.429688del
NM_001346813.1:c.4239delA
NM_001363725.2:c.1989del
NM_001371656.1:c.4368del
NM_001374820.1:c.4368del
NM_001374828.1:c.4488delMANE SELECT
NM_017519.3:c.4329del
NM_020732.3:c.4119delA
NM_175863.2:c.3906delA
NP_001333742.1:p.Lys1413Asnfs
NP_001350654.1:p.Lys663fs
NP_001358585.1:p.Lys1456fs
NP_001361749.1:p.Lys1456fs
NP_001361757.1:p.Lys1496fs
NP_059989.3:p.Lys1443fs
NP_065783.3:p.Lys1373Asnfs
NP_787059.2:p.Lys1302Asnfs
NC_000006.11:g.157521847del

Protein change:

K1443fs

Molecular consequence:

NM_001346813.1:c.4239delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363725.2:c.1989del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001371656.1:c.4368del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374820.1:c.4368del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374828.1:c.4488del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017519.3:c.4329del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020732.3:c.4119delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_175863.2:c.3906delA - 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

winged helix-turn-helix domain-containing protein [Burkholderia vietnamiensis]
winged helix-turn-helix domain-containing protein [Burkholderia vietnamiensis]
gi|2127773550|gnl|PRJNA231221|LK462 5|gb|UEB99764.1|

Protein
sensor histidine kinase [Burkholderia vietnamiensis]
sensor histidine kinase [Burkholderia vietnamiensis]
gi|2127773551|gnl|PRJNA231221|LK462 0|gb|UEB99765.1|

Protein

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
SCV002768186	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 2, 2020)	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

SCV002768186

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 2, 2020)

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	yes	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, SCV002768186.1

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

Description

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 18 of 20). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants predicted to cause NMD have been reported as pathogenic in individuals with Coffin-Siris syndrome (ClinVar). (P) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

#	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

Last Updated: Dec 24, 2022

ClinVar

Relating variation to medicine