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NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 6, 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:
RCV002444438.9

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)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002734110Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 6, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature.

Kosho T, Okamoto N, Ohashi H, Tsurusaki Y, Imai Y, Hibi-Ko Y, Kawame H, Homma T, Tanabe S, Kato M, Hiraki Y, Yamagata T, Yano S, Sakazume S, Ishii T, Nagai T, Ohta T, Niikawa N, Mizuno S, Kaname T, Naritomi K, Narumi Y, et al.

Am J Med Genet A. 2013 Jun;161A(6):1221-37. doi: 10.1002/ajmg.a.35933. Epub 2013 May 1. Review.

PubMed [citation]
PMID:
23637025
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002734110.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The c.1091_1093delAGA (p.K364del) alteration, located in coding exon 8 of the SMARCB1 gene, results from an in-frame deletion of 3 nucleotides at positions c.1091 toc.1093. This results in the deletion of 1 amino acid at codon 364. _x000D_ _x000D_ Based on the available evidence, the SMARCB1 c.1091_1093delAGA (p.K364del) alteration is classified as pathogenic for SMARCB1-related Coffin-Siris syndrome; however, its clinical significance for SMARCB1-related tumor predisposition syndrome is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals with a clinical diagnosis of Coffin-Siris syndrome, including several with confirmed de novo origin (Tsurusaki, 2012; Santen, 2013; Kosho, 2013; Kosho, 2014; Miyake, 2014; Sekiguchi, 2019). This amino acid position is highly conserved in available vertebrate species. In vitro and cell-based functional studies demonstrated this alteration results in reduced mSWI/SNF functional activity and is defective in generating DNA accessibility and in activating critical target genes (Valencia, 2019). This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024