NM_003072.5(SMARCA4):c.863C>T (p.Pro288Leu) AND Rhabdoid tumor predisposition syndrome 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 3, 2023
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:: RCV002550840.4

Allele description [Variation Report for NM_003072.5(SMARCA4):c.863C>T (p.Pro288Leu)]

NM_003072.5(SMARCA4):c.863C>T (p.Pro288Leu)

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.863C>T (p.Pro288Leu)

HGVS:

NC_000019.10:g.10987669C>T
NG_011556.2:g.31748C>T
NM_001128844.3:c.863C>T
NM_001128845.2:c.863C>T
NM_001128846.2:c.863C>T
NM_001128847.4:c.863C>T
NM_001128848.2:c.863C>T
NM_001128849.3:c.863C>T
NM_001374457.1:c.863C>T
NM_003072.5:c.863C>TMANE SELECT
NP_001122316.1:p.Pro288Leu
NP_001122317.1:p.Pro288Leu
NP_001122318.1:p.Pro288Leu
NP_001122319.1:p.Pro288Leu
NP_001122320.1:p.Pro288Leu
NP_001122321.1:p.Pro288Leu
NP_001361386.1:p.Pro288Leu
NP_003063.2:p.Pro288Leu
LRG_878t1:c.863C>T
LRG_878p1:p.Pro288Leu
NC_000019.9:g.11098345C>T
NC_000019.9:g.11098345C>T
NM_001128849.1:c.863C>T
NM_001128849.3:c.863C>T
NR_164683.1:n.1039C>T

Protein change:

P288L

Links:

dbSNP: rs1026742588

NCBI 1000 Genomes Browser:

rs1026742588

Molecular consequence:

NM_001128844.3:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128845.2:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128846.2:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128847.4:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128848.2:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128849.3:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374457.1:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003072.5:c.863C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_164683.1:n.1039C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003327290	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004204943	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 3, 2023)	unknown	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

SCV003327290

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 15, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004204943

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 3, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003327290.2

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 822621). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 288 of the SMARCA4 protein (p.Pro288Leu).

#	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 Baylor Genetics, SCV004204943.1

#	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: Sep 29, 2024

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