NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 26, 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:: RCV000377856.16

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]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Hylobates leucogenys rhadinovirus 2 DNA polymerase (dpol) gene, partial cds
Hylobates leucogenys rhadinovirus 2 DNA polymerase (dpol) gene, partial cds
gi|42495017|gb|AY465375.1|

Nucleotide
txid262584[Organism:noexp] (1)
Identical Protein Groups
262584[uid] (1)
Taxonomy

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329522	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (May 2, 2016)	germline	clinical testing	Citation Link,
SCV000761502	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22426308, 23815551, 23929686, 25533962, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329522

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(May 2, 2016)

germline

clinical testing

Citation Link,

SCV000761502

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2022)

germline

clinical testing

PubMed (5)
[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	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	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

Coffin-Siris syndrome is a SWI/SNF complex disorder.

Tsurusaki Y, Okamoto N, Ohashi H, Mizuno S, Matsumoto N, Makita Y, Fukuda M, Isidor B, Perrier J, Aggarwal S, Dalal AB, Al-Kindy A, Liebelt J, Mowat D, Nakashima M, Saitsu H, Miyake N, Matsumoto N.

Clin Genet. 2014 Jun;85(6):548-54. doi: 10.1111/cge.12225. Epub 2013 Jul 23.

PubMed [citation]

PMID:: 23815551

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000329522.6

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

Description

The c.1091_1093delAGA variant in the SMARCB1 gene is a recurrent pathogenic variant seen in individuals with Coffin-Siris syndrome (Tsurusaki et al., 2012; Santen et al., 2013; Kosho et al., 2014; Tsurusaki et al., 2014). The c.1091_1093delAGA variant causes an in-frame deletion of codon Lysine 364, denoted p.Lys364del. The c.1091_1093delAGA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1091_1093delAGA as a pathogenic variant.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000761502.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has been observed in individual(s) with clinical features of Coffin-Siris syndrome (PMID: 22426308, 23815551, 23929686, 25533962). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 30201). This variant is not present in population databases (gnomAD no frequency). This variant, c.1091_1093del, results in the deletion of 1 amino acid(s) of the SMARCB1 protein (p.Lys364del), but otherwise preserves the integrity of the reading frame.

#	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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