NM_007294.4(BRCA1):c.5152+20T>A AND not specified

Clinical significance:Benign (Last evaluated: Jun 20, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000123931.5

Allele description [Variation Report for NM_007294.4(BRCA1):c.5152+20T>A]

NM_007294.4(BRCA1):c.5152+20T>A

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5152+20T>A
HGVS:
  • NC_000017.11:g.43063854A>T
  • NG_005905.2:g.154130T>A
  • NM_007294.3:c.5152+20T>A
  • NM_007294.4:c.5152+20T>AMANE SELECT
  • NM_007297.4:c.5011+20T>A
  • NM_007298.3:c.1840+20T>A
  • NM_007299.4:c.1840+20T>A
  • NM_007300.4:c.5215+20T>A
  • LRG_292t1:c.5152+20T>A
  • LRG_292:g.154130T>A
  • NC_000017.10:g.41215871A>T
Links:
dbSNP: rs376836050
NCBI 1000 Genomes Browser:
rs376836050
Molecular consequence:
  • NM_007294.3:c.5152+20T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.4:c.5152+20T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.5011+20T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.1840+20T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.1840+20T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.5215+20T>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000167318GeneDxcriteria provided, single submitter
Benign
(May 9, 2014)
germlineclinical testing

Citation Link,

SCV000918724Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Jun 20, 2019)
germlineclinical testing

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

Citation Link,

SCV001973823Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedBenigngermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Denaturing high-performance liquid chromatography detects reliably BRCA1 and BRCA2 mutations.

Wagner T, Stoppa-Lyonnet D, Fleischmann E, Muhr D, Pag├Ęs S, Sandberg T, Caux V, Moeslinger R, Langbauer G, Borg A, Oefner P.

Genomics. 1999 Dec 15;62(3):369-76.

PubMed [citation]
PMID:
10644434

Diagnostic guidelines for high-resolution melting curve (HRM) analysis: an interlaboratory validation of BRCA1 mutation scanning using the 96-well LightScanner.

van der Stoep N, van Paridon CD, Janssens T, Krenkova P, Stambergova A, Macek M, Matthijs G, Bakker E.

Hum Mutat. 2009 Jun;30(6):899-909. doi: 10.1002/humu.21004.

PubMed [citation]
PMID:
19370767
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000167318.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918724.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: BRCA1 c.5152+20T>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 250844 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (0.00016 vs 0.001), allowing no conclusion about variant significance. c.5152+20T>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Wagner_1999), however in one case the variant was present in both an affected and unaffected family member, which provides supporting evidence for a benign role of this variant, although the age of the family members was not provided (Mohammadi_2009). Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.7235insG via UMD; BRCA1 c.68_69delAG from an internal specimen; and BRCA1 c.5152+2T>G from an internal specimen), providing supporting evidence for a benign role. Additionally, the variant has been reported in our lab in a patient as homozygous. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as a benign variant.

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973823.1

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

Last Updated: Nov 10, 2021

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