NM_003072.5(SMARCA4):c.4251C>A (p.Ser1417Arg) AND Rhabdoid tumor predisposition syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 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:: RCV000819155.7

Allele description [Variation Report for NM_003072.5(SMARCA4):c.4251C>A (p.Ser1417Arg)]

NM_003072.5(SMARCA4):c.4251C>A (p.Ser1417Arg)

Gene:

SMARCA4:SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_003072.5(SMARCA4):c.4251C>A (p.Ser1417Arg)

HGVS:

NC_000019.10:g.11041387C>A
NG_011556.3:g.85456C>A
NM_001128844.3:c.4251C>A
NM_001128845.2:c.4161C>A
NM_001128846.2:c.4161C>A
NM_001128847.4:c.4152C>A
NM_001128848.2:c.4152C>A
NM_001128849.3:c.4347C>A
NM_001374457.1:c.4152C>A
NM_001387283.1:c.4347C>A
NM_003072.5:c.4251C>AMANE SELECT
NP_001122316.1:p.Ser1417Arg
NP_001122317.1:p.Ser1387Arg
NP_001122318.1:p.Ser1387Arg
NP_001122319.1:p.Ser1384Arg
NP_001122320.1:p.Ser1384Arg
NP_001122321.1:p.Ser1449Arg
NP_001361386.1:p.Ser1384Arg
NP_001374212.1:p.Ser1449Arg
NP_003063.2:p.Ser1417Arg
LRG_878t1:c.4251C>A
LRG_878:g.85456C>A
LRG_878p1:p.Ser1417Arg
NC_000019.9:g.11152063C>A
NG_011556.2:g.85466C>A
NM_001128849.1:c.4347C>A
NR_164683.1:n.4641C>A

Protein change:

S1384R

Links:

dbSNP: rs377057304

NCBI 1000 Genomes Browser:

rs377057304

Molecular consequence:

NM_001128844.3:c.4251C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128845.2:c.4161C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128846.2:c.4161C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128847.4:c.4152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128848.2:c.4152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128849.3:c.4347C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374457.1:c.4152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001387283.1:c.4347C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003072.5:c.4251C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164683.1:n.4641C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Rhabdoid tumor predisposition syndrome 2 (RTPS2)
Identifiers:: MONDO: MONDO:0013224; MedGen: C2750074; Orphanet: 231108; Orphanet: 69077; OMIM: 613325

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Mrpl17 protein [Mus musculus]
Mrpl17 protein [Mus musculus]
gi|14715101|gb|AAH10718.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000959800	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2023)	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

SCV000959800

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 2023)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959800.4

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

Description

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1449 of the SMARCA4 protein (p.Ser1449Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMARCA4 protein function. ClinVar contains an entry for this variant (Variation ID: 661681). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions.

#	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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