NM_007294.3(BRCA1):c.4964_4982del19 (p.Ser1655Tyrfs) AND Hereditary breast and ovarian cancer syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 18, 2017
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:: RCV000123279.3

Allele description

NM_007294.3(BRCA1):c.4964_4982del19 (p.Ser1655Tyrfs)

Gene:

BRCA1:BRCA1, DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.3(BRCA1):c.4964_4982del19 (p.Ser1655Tyrfs)

HGVS:

NC_000017.11:g.43070932_43070950del19
NG_005905.2:g.147034_147052del19
NM_007294.3:c.4964_4982del19
NP_009225.1:p.Ser1655Tyrfs
LRG_292t1:c.4964_4982del19
LRG_292:g.147034_147052del19
LRG_292p1:p.Ser1655Tyrfs
NC_000017.10:g.41222949_41222967del
NC_000017.10:g.41222949_41222967del19
NM_007294.3:c.4964_4982del
NM_007294.3:c.4964_4982delCTGGCCTGACCCCAGAAGA
NR_027676.1:n.5100_5118del19
U14680.1:n.5083_5101del19
p.S1655YFS*16
p.S1655YfsX16
p.Ser1655Tyrfs*16

Nucleotide change:

5083del19

Links:

Breast Cancer Information Core (BIC) (BRCA1): 5083&base_change=del 19; dbSNP: rs80359876

NCBI 1000 Genomes Browser:

rs80359876

Molecular consequence:

NM_007294.3:c.4964_4982del19 - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027676.1:n.5100_5118del19 - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:: Hereditary breast and ovarian cancer
Identifiers:: MedGen: C0677776; Orphanet: 145
Prevalence:: http://www.ncbi.nlm.nih.gov/books/NBK1247/ https://www.ncbi.nlm.nih.gov/books/NBK1247

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000166586	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2016)	germline	clinical testing	Citation Link,
SCV000586905	Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency - The Canadian Open Genetics Repository (COGR)	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 18, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000587436	Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Pathogenic (Jan 31, 2014)	germline	research

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000166586

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2016)

germline

clinical testing

Citation Link,

SCV000586905

Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency - The Canadian Open Genetics Repository (COGR)

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 18, 2017)

germline

clinical testing

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

SCV000587436

Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)

no assertion criteria provided

Pathogenic
(Jan 31, 2014)

germline

research

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	research
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 Invitae, SCV000166586.3

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

Description

This sequence change deletes 19 nucleotides from exon 15 of the BRCA1 mRNA (c.4964_4982del19), causing a frameshift at codon 1655. This creates a premature translational stop signal (p.Ser1655Tyrfs*16) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in individuals and families affected with breast and ovarian cancer (PMID: 9145677, 26219728, 16847550, 18159056, 26681312). This variant is commonly reported in affected individuals of Calabrian or Sicilian descent (PMID: 11462242, 23199084, 11938448, 17221156). This variant is also known as 5083del19 in the literature. 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

From Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency - The Canadian Open Genetics Repository (COGR), SCV000586905.1

#	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 Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587436.1

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

Last Updated: Aug 19, 2017

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