NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del) AND Intellectual disability, autosomal dominant 15

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Sep 2, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000023121.24

Allele description [Variation Report for NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)]

NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)

Gene:

SMARCB1:SWI/SNF related BAF chromatin remodeling complex subunit B1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

22q11.23

Genomic location:

Preferred name:

NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)

HGVS:

NC_000022.10:g.24175857_24175859del
NC_000022.11:g.23833670AGA[2]
NG_009303.1:g.51708AGA[2]
NM_001007468.3:c.1058AGA[2]
NM_001317946.2:c.1112AGA[2]
NM_001362877.2:c.1139AGA[2]
NM_003073.5:c.1085AGA[2]MANE SELECT
NP_001007469.1:p.Lys355del
NP_001304875.1:p.Lys373del
NP_001349806.1:p.Lys382del
NP_003064.2:p.Lys364del
NP_003064.2:p.Lys364del
LRG_520t1:c.1091_1093del
LRG_520:g.51708AGA[2]
LRG_520p1:p.Lys364del
NC_000022.10:g.24175857AGA[2]
NC_000022.10:g.24175857_24175859del
NC_000022.10:g.24175857_24175859delAGA
NM_003073.3:c.1091_1093del
NM_003073.3:c.1091_1093delAGA
NM_003073.5:c.1091_1093delMANE SELECT

Protein change:

K355del

Links:

OMIM: 601607.0012; dbSNP: rs875989800

NCBI 1000 Genomes Browser:

rs875989800

Molecular consequence:

NM_001007468.3:c.1058AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001317946.2:c.1112AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001362877.2:c.1139AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_003073.5:c.1085AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: Intellectual disability, autosomal dominant 15 (CSS3)
Synonyms:: COFFIN-SIRIS SYNDROME 3
Identifiers:: MONDO: MONDO:0013820; MedGen: C3553248; Orphanet: 1465; OMIM: 614608

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044412	OMIM	no assertion criteria provided	Pathogenic (Mar 18, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000268063	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 25168959, 23556151
SCV000680384	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Sep 8, 2017)	de novo	clinical testing	Citation Link,
SCV000999275	Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001244989	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31759698, 25741868
SCV003835181	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 11, 2021)	unknown	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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	de novo	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome.

Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, et al.

Nat Genet. 2012 Mar 18;44(4):376-8. doi: 10.1038/ng.2219.

PubMed [citation]

PMID:: 22426308

Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A.

Kosho T, Okamoto N; Coffin-Siris Syndrome International Collaborators..

Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75. doi: 10.1002/ajmg.c.31407. Epub 2014 Aug 28.

PubMed [citation]

PMID:: 25168959

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000044412.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 3 patients (patients 4, 21, and 22) with Coffin-Siris syndrome (CSS3; 614608), Tsurusaki et al. (2012) identified a heterozygous 3-bp in-frame deletion in the SMARCB1 gene (1091_1093delAGA) that resulted in deletion of lysine-364 (lys364del). The mutation was de novo in 2 cases, and parental samples were unavailable in the third. This mutation was not seen in any of 502 Japanese control chromosomes.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000268063.3

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

Description

Recurrent de novo pathogenic variant; affected persons had strikingly similar clinical manifestations.

#	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

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV000680384.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	1	blood	not provided		1	not provided	not provided	not provided

From Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, SCV000999275.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001244989.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, loss of function and gain of function are all known mechanisms of disease in this gene. Loss of function variants are associated with cancer susceptibility (rhabdoid tumor predisposition syndrome 1 (MIM#609322), schwannomatosis-1 (MIM#162091), rhabdoid tumors somatic (MIM#609322)). An inframe deletion variant, missense variants and truncating variants escaping nonsense-mediated decay have been reported to have either a gain of function or dominant negative mechanism, and are all associated with Coffin-Siris syndrome 3 (MIM#614608) (OMIM, PMID: 31759698). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0213 - In-frame insertion/deletion in a non-repetitive region that has high conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (DECIPHER, PMID: 31759698). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported multiple times as pathogenic and de novo in individuals with Coffin-Siris syndrome (PMID: 31759698, ClinVar, DECIPHER). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting 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

From Baylor Genetics, SCV003835181.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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