NM_004656.4(BAP1):c.1811T>C (p.Val604Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 13, 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:: RCV003585928.2

Allele description [Variation Report for NM_004656.4(BAP1):c.1811T>C (p.Val604Ala)]

NM_004656.4(BAP1):c.1811T>C (p.Val604Ala)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_004656.4(BAP1):c.1811T>C (p.Val604Ala)

HGVS:

NC_000003.12:g.52403217A>G
NG_031859.1:g.11777T>C
NM_001410772.1:c.1757T>C
NM_004656.4:c.1811T>CMANE SELECT
NP_001397701.1:p.Val586Ala
NP_004647.1:p.Val604Ala
NP_004647.1:p.Val604Ala
LRG_529t1:c.1811T>C
LRG_529:g.11777T>C
LRG_529p1:p.Val604Ala
NC_000003.11:g.52437233A>G
NM_004656.2:c.1811T>C
NM_004656.2:c.1811T>C

Protein change:

V586A

Molecular consequence:

NM_001410772.1:c.1757T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004656.4:c.1811T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004362525	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005095126	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 13, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004362525

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 24, 2022)

germline

clinical testing

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

SCV005095126

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 13, 2024)

germline

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

Citations

PubMed

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 Color Diagnostics, LLC DBA Color Health, SCV004362525.1

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

Description

This missense variant replaces valine with alanine at codon 604 of the BAP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BAP1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 Ambry Genetics, SCV005095126.1

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

Description

The p.V604A variant (also known as c.1811T>C), located in coding exon 14 of the BAP1 gene, results from a T to C substitution at nucleotide position 1811. The valine at codon 604 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

#	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: Aug 11, 2024

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