NM_000059.4(BRCA2):c.4139_4140dup (p.Lys1381fs) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jul 31, 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:: RCV000483206.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.4139_4140dup (p.Lys1381fs)]

NM_000059.4(BRCA2):c.4139_4140dup (p.Lys1381fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.4139_4140dup (p.Lys1381fs)

Other names:

4366insTT

HGVS:

NC_000013.11:g.32338494_32338495dup
NG_012772.3:g.28015_28016dup
NM_000059.4:c.4139_4140dupMANE SELECT
NM_000059.4:c.4139_4140dupTT
NP_000050.3:p.Lys1381fs
LRG_293:g.28015_28016dup
NC_000013.10:g.32912630_32912631insTT
NC_000013.10:g.32912631_32912632dup
NM_000059.3:c.4139_4140dupTT
NM_000059.4:c.4139_4140dup
U43746.1:n.4366_4367insTT
p.K1381Lfs*8

Protein change:

K1381fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 4366&base_change=ins TT; dbSNP: rs276174842

NCBI 1000 Genomes Browser:

rs276174842

Molecular consequence:

NM_000059.4:c.4139_4140dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Protein
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566994	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 10, 2015)	germline	clinical testing	Citation Link,
SCV000889044	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 28, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005090031	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005199103	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

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 GeneDx, SCV000566994.2

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

Description

This duplication of 2 nucleotides in BRCA2 is denoted c.4139_4140dupTT at the cDNA level and p.Lys1381LeufsX8 (K1381LfsX8) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CAGA[TT]AAAG. The duplication causes a frameshift, which changes a Lysine to a Leucine at codon 1381, and creates a premature stop codon at position 8 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.4139_4140dupTT has been reported in at least one family with multiple cases of breast cancer (Levanat 2012). we consider this variant to be pathogenic.

#	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, SCV000889044.2

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

#	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 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090031.1

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

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199103.1

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

#	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

Last Updated: Nov 3, 2024

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