NM_004656.4(BAP1):c.1649del (p.Val550fs) AND BAP1-related tumor predisposition syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 30, 2024
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:: RCV002594290.4

Allele description [Variation Report for NM_004656.4(BAP1):c.1649del (p.Val550fs)]

NM_004656.4(BAP1):c.1649del (p.Val550fs)

Gene:

BAP1:BRCA1 associated deubiquitinase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_004656.4(BAP1):c.1649del (p.Val550fs)

HGVS:

NC_000003.12:g.52403496del
NG_031859.1:g.11498del
NM_001410772.1:c.1595delT
NM_004656.4:c.1649delMANE SELECT
NP_001397701.1:p.Val532Alafs
NP_004647.1:p.Val550Alafs
NP_004647.1:p.Val550fs
LRG_529t1:c.1649del
LRG_529:g.11498del
LRG_529p1:p.Val550Alafs
NC_000003.11:g.52437512del
NM_004656.2:c.1649delT

Protein change:

V550fs

Molecular consequence:

NM_001410772.1:c.1595delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004656.4:c.1649del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: BAP1-related tumor predisposition syndrome (TPDS1)
Synonyms:: Tumor predisposition syndrome; Tumor susceptibility linked to germline BAP1 mutations; BAP1 tumor predisposition syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013692; MedGen: C3280492; Orphanet: 289539; OMIM: 614327

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002954996	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21874000, 23684012, 28492532
SCV005083631	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Apr 30, 2024)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002954996

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 22, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005083631

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Apr 30, 2024)

unknown

clinical testing

Citation Link

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

Germline BAP1 mutations predispose to malignant mesothelioma.

Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M.

Nat Genet. 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912.

PubMed [citation]

PMID:: 21874000
PMCID:: PMC3184199

Germline BAP1 mutations predispose to renal cell carcinomas.

Popova T, Hebert L, Jacquemin V, Gad S, Caux-Moncoutier V, Dubois-d'Enghien C, Richaudeau B, Renaudin X, Sellers J, Nicolas A, Sastre-Garau X, Desjardins L, Gyapay G, Raynal V, Sinilnikova OM, Andrieu N, Manié E, de Pauw A, Gesta P, Bonadona V, Maugard CM, Penet C, et al.

Am J Hum Genet. 2013 Jun 6;92(6):974-80. doi: 10.1016/j.ajhg.2013.04.012. Epub 2013 May 16.

PubMed [citation]

PMID:: 23684012
PMCID:: PMC3675229

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002954996.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with BAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val550Alafs*21) in the BAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAP1 are known to be pathogenic (PMID: 21874000, 23684012). For these reasons, this variant has been classified as Pathogenic.

#	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 Myriad Genetics, Inc., SCV005083631.1

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

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	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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