NM_000059.4(BRCA2):c.4211C>A (p.Ser1404Ter) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 24, 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:: RCV000560709.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.4211C>A (p.Ser1404Ter)]

NM_000059.4(BRCA2):c.4211C>A (p.Ser1404Ter)

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.4211C>A (p.Ser1404Ter)

HGVS:

NC_000013.11:g.32338566C>A
NG_012772.3:g.28087C>A
NM_000059.4:c.4211C>AMANE SELECT
NP_000050.2:p.Ser1404Ter
NP_000050.3:p.Ser1404Ter
LRG_293t1:c.4211C>A
LRG_293:g.28087C>A
LRG_293p1:p.Ser1404Ter
NC_000013.10:g.32912703C>A
NM_000059.3:c.4211C>A

Protein change:

S1404*

Links:

dbSNP: rs41293489

NCBI 1000 Genomes Browser:

rs41293489

Molecular consequence:

NM_000059.4:c.4211C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

Recent activity

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"51019-43-3"[CompleteSynonym] (1)
PubChem Compound
Zinc finger protein 11, partial [Cucurbita argyrosperma subsp. sororia]
Zinc finger protein 11, partial [Cucurbita argyrosperma subsp. sororia]
gi|2047897486|gb|KAG6571507.1||gnl| AGKQH|SDJN03_28235

Protein
Structure-specific endonuclease subunit SLX1, partial [Cucurbita argyrosperma su...
Structure-specific endonuclease subunit SLX1, partial [Cucurbita argyrosperma subsp. argyrosperma]
gi|2053600282|gb|KAG7019098.1||gnl| DJN|SDJN02_18056

Protein
uncharacterized protein LOC111443053 isoform X4 [Cucurbita moschata]
uncharacterized protein LOC111443053 isoform X4 [Cucurbita moschata]
gi|1279767761|ref|XP_022936431.1|

Protein
JGI_XZT9481.fwd NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7587358 5',...
JGI_XZT9481.fwd NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7587358 5', mRNA sequence
gi|57043162|gnl|dbEST|26935719|gb|C 55.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000635351	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 24, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20104584, 25151137, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000635351

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 24, 2023)

germline

clinical testing

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

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

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing.

Guan Y, Hu H, Peng Y, Gong Y, Yi Y, Shao L, Liu T, Li G, Wang R, Dai P, Bignon YJ, Xiao Z, Yang L, Mu F, Xiao L, Xie Z, Yan W, Xu N, Zhou D, Yi X.

Fam Cancer. 2015 Mar;14(1):9-18. doi: 10.1007/s10689-014-9749-9.

PubMed [citation]

PMID:: 25151137

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000635351.4

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

Description

This sequence change creates a premature translational stop signal (p.Ser1404*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). A different variant (c.4211C>G) giving rise to the same protein effect has been determined to be pathogenic (PMID: 25151137). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 462333). 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

Last Updated: Sep 29, 2024

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