NM_000059.4(BRCA2):c.721A>T (p.Lys241Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 22, 2022
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:: RCV000219810.8

Allele description [Variation Report for NM_000059.4(BRCA2):c.721A>T (p.Lys241Ter)]

NM_000059.4(BRCA2):c.721A>T (p.Lys241Ter)

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.721A>T (p.Lys241Ter)

HGVS:

NC_000013.11:g.32330958A>T
NG_012772.3:g.20479A>T
NM_000059.4:c.721A>TMANE SELECT
NP_000050.2:p.Lys241Ter
NP_000050.3:p.Lys241Ter
LRG_293t1:c.721A>T
LRG_293:g.20479A>T
LRG_293p1:p.Lys241Ter
NC_000013.10:g.32905095A>T
NM_000059.3:c.721A>T

Protein change:

K241*

Links:

dbSNP: rs876659100

NCBI 1000 Genomes Browser:

rs876659100

Molecular consequence:

NM_000059.4:c.721A>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000275154	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 17, 2015)	germline	clinical testing	Citation Link,
SCV000904829	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 3378028, 32862574, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000275154

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 17, 2015)

germline

clinical testing

Citation Link,

SCV000904829

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 22, 2022)

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

Angioid streaks in beta thalassaemia minor.

Kinsella FP, Mooney DJ.

Br J Ophthalmol. 1988 Apr;72(4):303-4.

PubMed [citation]

PMID:: 3378028
PMCID:: PMC1041438

Genetic screening results of individuals with high risk BRCA-related breast/ovarian cancer in Trakya region of Turkey.

Demir S, Tozkir H, Gurkan H, Atli EI, Yalcintepe S, Atli E, Sezer YA, Eker D, Tuncbilek N, Tastekin E, Ozen Y, Cicin I.

J BUON. 2020 May-Jun;25(3):1337-1347.

PubMed [citation]

PMID:: 32862574

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000275154.5

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

Description

The p.K241* pathogenic mutation (also known as c.721A>T) located in coding exon 8 of the BRCA2 gene, results from an A to T substitution at nucleotide position 721. This changes the amino acid from a lysine to a stop codon within coding exon 8. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

#	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 Color Diagnostics, LLC DBA Color Health, SCV000904829.4

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

Description

This variant changes 1 nucleotide in exon 9 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast cancer (PMID: 32862574, 3378028). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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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