NM_007294.3(BRCA1):c.3752_3755GTCT[1] (p.Ser1253fs) AND Breast-ovarian cancer, familial 1

Clinical significance:Pathogenic (Last evaluated: Apr 22, 2016)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
12 submissions [Details]
Record status:
current
Accession:
RCV000019242.17

Allele description

NM_007294.3(BRCA1):c.3752_3755GTCT[1] (p.Ser1253fs)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.3752_3755GTCT[1] (p.Ser1253fs)
Other names:
3874del4; 3875_3878delGTCT
HGVS:
  • NC_000017.11:g.43091773_43091776GACA[1]
  • NG_005905.2:g.126205_126208GTCT[1]
  • NM_007294.3:c.3752_3755GTCT[1]
  • NM_007294.3:c.3756_3759delGTCT
  • NM_007297.4:c.3611_3614GTCT[1]
  • NM_007298.3:c.788-743_788-740del
  • NM_007299.4:c.788-743_788-740del
  • NM_007300.4:c.3752_3755GTCT[1]
  • NP_009225.1:p.Ser1253fs
  • NP_009228.2:p.Ser1206fs
  • NP_009231.2:p.Ser1253fs
  • LRG_292t1:c.3756_3759del
  • LRG_292:g.126209_126212del
  • LRG_292p1:p.Ser1253fs
  • NC_000017.10:g.41243789_41243792delAGAC
  • NC_000017.10:g.41243790_41243793GACA[1]
  • NR_027676.1:n.3888_3891GTCT[1]
  • U14680.1:c.3756_3759del
  • U14680.1:n.3875_3878delGTCT
  • p.S1253Rfs*10
  • p.S1253RfsX10
  • p.Ser1253Argfs*10
Nucleotide change:
3875del4
Links:
Breast Cancer Information Core (BIC) (BRCA1): 3874&base_change=del TGTC; Breast Cancer Information Core (BIC) (BRCA1): 3875&base_change=del GTCT; OMIM: 113705.0014; dbSNP: rs80357868
NCBI 1000 Genomes Browser:
rs80357868
Molecular consequence:
  • NM_007294.3:c.3756_3759delGTCT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007297.4:c.3611_3614GTCT[1] - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007300.4:c.3752_3755GTCT[1] - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007298.3:c.788-743_788-740del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.788-743_788-740del - intron variant - [Sequence Ontology: SO:0001627]
Observations:
236

Condition(s)

Name:
Breast-ovarian cancer, familial 1 (BROVCA1)
Synonyms:
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; OVARIAN CANCER, SUSCEPTIBILITY TO; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; See all synonyms [MedGen]
Identifiers:
MedGen: C2676676; Orphanet: 145; OMIM: 604370

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000039530OMIMno assertion criteria providedPathogenic
(Dec 1, 1994)
germlineliterature only

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

SCV000053723Sharing Clinical Reports Project (SCRP)no assertion criteria providedPathogenic
(Nov 19, 2013)
germlineclinical testing

SCV000144861Breast Cancer Information Core (BIC) (BRCA1)no assertion criteria providedPathogenic
(May 29, 2002)
germlineclinical testing

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

SCV000212000Division Human Genetics,Medical University Innsbruck - BRCA-Tyrolno assertion criteria provided
    Pathogenic
    (Feb 11, 2015)
    germlineclinical testing

    SCV000220913Counsylcriteria provided, single submitter
    Likely pathogenic
    (Nov 24, 2014)
    unknownliterature only

    PubMed (12)
    [See all records that cite these PMIDs]

    Counsyl Autosomal Dominant Disease Classification criteria (2015),

    Citation Link,

    SCV000282317Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)reviewed by expert panel
    Pathogenic
    (Apr 22, 2016)
    germlinecuration

    ENIGMA BRCA1/2 Classification Criteria (2015),

    Citation Link,

    SCV000325742Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridgecriteria provided, single submitter
    Pathogenic
    (Oct 2, 2015)
    germlineclinical testing

    CIMBA_Mutation_Classification_guidelines_May16.pdf,

    Citation Link,

    SCV000564358Department of Medical Genetics,Oslo University Hospitalcriteria provided, single submitter
    Pathogenic
    (Feb 10, 2015)
    germlineclinical testing

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

    SCV000577928Genologica Medica

    See additional submitters

    criteria provided, single submitter
    Pathogenic
    (Jan 1, 2017)
    germlineclinical testing

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

    SCV000733618Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensusno assertion criteria providedPathogenicgermlineclinical testing

    SCV000744625DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensuscriteria provided, single submitter
    Pathogenic
    (Sep 21, 2015)
    germlineclinical testing

    Citation Link,

    SCV000839892Human Genome Sequencing Center Clinical Lab,Baylor College of Medicinecriteria provided, single submitter
    Pathogenic
    (Nov 1, 2017)
    germlineclinical testing

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

    Description

    BRCA-mutation spectrum Western Austria

    SCV000212000

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlineyes84not providednot providednot providednot providedclinical testing
    not providedgermlinenot provided47not providednot provided47not providedliterature only, clinical testing
    not providedgermlineunknownnot provided232not providednot providednot providedclinical testing, curation
    not providedunknownunknownnot providednot providednot providednot providednot providedliterature only
    Africangermlineyes2not providednot providednot providednot providedclinical testing
    Asiangermlineyes1not providednot providednot providednot providedclinical testing
    Caucasiangermlineyes10not providednot providednot providednot providedclinical testing
    Causasiansgermlineyesnot provided4not providednot providedyesclinical testing
    Central/Eastern Europeangermlineyes2not providednot providednot providednot providedclinical testing
    Central/Eastern European, Latin Americangermlineyes1not providednot providednot providednot providedclinical testing
    English, French, Irish, Scottish, Germangermlineyes1not providednot providednot providednot providedclinical testing
    Irishgermlineyes1not providednot providednot providednot providedclinical testing
    Italiangermlineyes2not providednot providednot providednot providedclinical testing
    Western Europeangermlineyes38not providednot providednot providednot providedclinical testing
    Western European, Italiangermlineyes2not providednot providednot providednot providedclinical testing
    Western European, Norwegiangermlineyes1not providednot providednot providednot providedclinical testing
    Western Europeanan, Central/Eastern Europeangermlineyes1not providednot providednot providednot providedclinical testing

    Citations

    PubMed

    BRCA1 and BRCA2 mutations in women with familial or early-onset breast/ovarian cancer in the Czech Republic.

    Foretova L, Machackova E, Navratilova M, Pavlu H, Hruba M, Lukesova M, Valik D.

    Hum Mutat. 2004 Apr;23(4):397-8.

    PubMed [citation]
    PMID:
    15024741

    BRCA1 mutations in a population-based sample of young women with breast cancer.

    Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA.

    N Engl J Med. 1996 Jan 18;334(3):137-42.

    PubMed [citation]
    PMID:
    8531967
    See all PubMed Citations (14)

    Details of each submission

    From OMIM, SCV000039530.2

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (1)

    Description

    Castilla et al. (1994) studied 50 probands with a family history of breast and/or ovarian cancer (604370) for germline mutations in the coding region of the BRCA1 candidate gene. They identified a 4-bp deletion at position 3875, leading to a premature termination codon at position 1252 and a truncated protein.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

    From Sharing Clinical Reports Project (SCRP), SCV000053723.6

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlinenot provided47not providednot providednot providednot providednot provided See 1

    Co-occurrences

    #ZygosityAllelesNumber of Observations
    1SingleHeterozygoteBRCA2:668A>T (Q147L)1

    From Breast Cancer Information Core (BIC) (BRCA1), SCV000144861.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided61not providednot providedclinical testing PubMed (1)
    2not provided2not providednot providedclinical testing PubMed (1)
    3not provided2not providednot providedclinical testing PubMed (1)
    4not provided5not providednot providedclinical testing PubMed (1)
    5not provided1not providednot providedclinical testing PubMed (1)
    6African2not providednot providedclinical testing PubMed (1)
    7Asian1not providednot providedclinical testing PubMed (1)
    8Caucasian6not providednot providedclinical testing PubMed (1)
    9Caucasian1not providednot providedclinical testing PubMed (1)
    10Caucasian2not providednot providedclinical testing PubMed (1)
    11Caucasian1not providednot providedclinical testing PubMed (1)
    12Central/Eastern European2not providednot providedclinical testing PubMed (1)
    13Central/Eastern European, Latin American1not providednot providedclinical testing PubMed (1)
    14English, French, Irish, Scottish, German1not providednot providedclinical testing PubMed (1)
    15Irish1not providednot providedclinical testing PubMed (1)
    16Italian2not providednot providedclinical testing PubMed (1)
    17Western European38not providednot providedclinical testing PubMed (1)
    18Western European, Italian2not providednot providedclinical testing PubMed (1)
    19Western European, Norwegian1not providednot providedclinical testing PubMed (1)
    20Western Europeanan, Central/Eastern European1not providednot providedclinical testing PubMed (1)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided61not providednot providednot provided
    2germlineyesnot providednot providednot provided2not providednot providednot provided
    3germlineyesnot providednot providednot provided2not providednot providednot provided
    4germlineyesnot providednot providednot provided5not providednot providednot provided
    5germlineyesnot providednot providednot provided1not providednot providednot provided
    6germlineyesnot providednot providednot provided2not providednot providednot provided
    7germlineyesnot providednot providednot provided1not providednot providednot provided
    8germlineyesnot providednot providednot provided6not providednot providednot provided
    9germlineyesnot providednot providednot provided1not providednot providednot provided
    10germlineyesnot providednot providednot provided2not providednot providednot provided
    11germlineyesnot providednot providednot provided1not providednot providednot provided
    12germlineyesnot providednot providednot provided2not providednot providednot provided
    13germlineyesnot providednot providednot provided1not providednot providednot provided
    14germlineyesnot providednot providednot provided1not providednot providednot provided
    15germlineyesnot providednot providednot provided1not providednot providednot provided
    16germlineyesnot providednot providednot provided2not providednot providednot provided
    17germlineyesnot providednot providednot provided38not providednot providednot provided
    18germlineyesnot providednot providednot provided2not providednot providednot provided
    19germlineyesnot providednot providednot provided1not providednot providednot provided
    20germlineyesnot providednot providednot provided1not providednot providednot provided

    From Division Human Genetics,Medical University Innsbruck - BRCA-Tyrol, SCV000212000.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided3not providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided3not providednot providednot provided

    From Counsyl, SCV000220913.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (12)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

    From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000282317.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedcurationnot provided

    Description

    Variant allele predicted to encode a truncated non-functional protein.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

    From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000325742.3

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineunknownnot providednot providednot providednot providednot provided232not provided

    From Department of Medical Genetics,Oslo University Hospital, SCV000564358.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided10not providednot providedclinical testing PubMed (1)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided10not providednot providednot provided

    From Genologica Medica, SCV000577928.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1Causasiansnot providednot providedyesclinical testing PubMed (1)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providedBloodnot providednot providednot provided4not provided

    From Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus, SCV000733618.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot providednot providednot providednot providednot provided

    From DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus, SCV000744625.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot providednot providednot providednot providednot provided

    From Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine, SCV000839892.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (1)

    Description

    The c.3756_3759delGTCT (p.Ser1253Argfs*10) frame shift variant is predicted to yield loss of function transcripts/proteins of BRCA1 gene, which is one of mechanisms causing BRCA1 defect related cancers. This variant is extremely rare in general population (4 in 246010 by gnomad) and observed in multiple breast/ovarian cancer patients (PMID:78944991, 12947551, 21324516, 23633455, 24504028). It has been also observed in other clinical labs and reported as pathogenic. Based on the above evidences, we interpret this variant as pathogenic.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

    Last Updated: Sep 15, 2019

    Support Center