NM_000059.4(BRCA2):c.136C>T (p.Pro46Ser) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 5, 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:: RCV000588395.30

Allele description [Variation Report for NM_000059.4(BRCA2):c.136C>T (p.Pro46Ser)]

NM_000059.4(BRCA2):c.136C>T (p.Pro46Ser)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.136C>T (p.Pro46Ser)

HGVS:

NC_000013.11:g.32319145C>T
NG_012772.3:g.8666C>T
NG_017006.2:g.1219G>A
NM_000059.4:c.136C>TMANE SELECT
NP_000050.2:p.Pro46Ser
NP_000050.3:p.Pro46Ser
LRG_293t1:c.136C>T
LRG_293:g.8666C>T
LRG_293p1:p.Pro46Ser
NC_000013.10:g.32893282C>T
NM_000059.3:c.136C>T
U43746.1:n.364C>T
p.P46S

Protein change:

P46S

Links:

dbSNP: rs80358425

NCBI 1000 Genomes Browser:

rs80358425

Molecular consequence:

NM_000059.4:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Homo sapiens BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast) (BUB3)...
Homo sapiens BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast) (BUB3), mRNA
gi|4757879|ref|NM_004725.1|

Nucleotide
Rattus norvegicus golgin A2 (Golga2), mRNA
Rattus norvegicus golgin A2 (Golga2), mRNA
gi|399154160|ref|NM_022596.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000617114	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 22, 2022)	germline	clinical testing	Citation Link,
SCV000888976	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jan 5, 2023)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12491487, 26214590, 29884841, 31853058, 35979650, 31911673, 26467025
SCV001334479	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Mar 1, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000617114

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 22, 2022)

germline

clinical testing

Citation Link,

SCV000888976

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jan 5, 2023)

unknown

clinical testing

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

SCV001334479

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Mar 1, 2020)

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	yes	1	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

Breast cancer genetics in African Americans.

Olopade OI, Fackenthal JD, Dunston G, Tainsky MA, Collins F, Whitfield-Broome C.

Cancer. 2003 Jan 1;97(1 Suppl):236-45. Review.

PubMed [citation]

PMID:: 12491487

Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas.

Krauthammer M, Kong Y, Bacchiocchi A, Evans P, Pornputtapong N, Wu C, McCusker JP, Ma S, Cheng E, Straub R, Serin M, Bosenberg M, Ariyan S, Narayan D, Sznol M, Kluger HM, Mane S, Schlessinger J, Lifton RP, Halaban R.

Nat Genet. 2015 Sep;47(9):996-1002. doi: 10.1038/ng.3361. Epub 2015 Jul 27.

PubMed [citation]

PMID:: 26214590
PMCID:: PMC4916843

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000617114.3

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 364C>T; This variant is associated with the following publications: (PMID: 29884841, 12491487, 26214590, 32377563, 31853058)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888976.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The frequency of this variant in the general population, 0.00016 (4/24934 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual affected with breast cancer (PMID: 12491487 (2003)) and as a somatic variant identified in a melanoma tumor (PMID: 26214590 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV001334479.25

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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