NM_007294.4(BRCA1):c.5564del (p.Ile1855fs) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Apr 17, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000589978.1

Allele description [Variation Report for NM_007294.4(BRCA1):c.5564del (p.Ile1855fs)]

NM_007294.4(BRCA1):c.5564del (p.Ile1855fs)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5564del (p.Ile1855fs)
HGVS:
  • NC_000017.11:g.43045706del
  • NG_005905.2:g.172278del
  • NM_007294.4:c.5564delMANE SELECT
  • NM_007297.4:c.5423del
  • NM_007298.3:c.2252del
  • NM_007299.4:c.*78del
  • NM_007300.4:c.5627del
  • NP_009225.1:p.Ile1855fs
  • NP_009228.2:p.Ile1808fs
  • NP_009229.2:p.Ile751fs
  • NP_009231.2:p.Ile1876fs
  • LRG_292:g.172278del
  • NC_000017.10:g.41197723del
  • NM_007294.3:c.5564delT
  • NR_027676.2:n.5741del
Protein change:
I1808fs
Links:
dbSNP: rs1555574355
NCBI 1000 Genomes Browser:
rs1555574355
Molecular consequence:
  • NM_007299.4:c.*78del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_007294.4:c.5564del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007297.4:c.5423del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007298.3:c.2252del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007300.4:c.5627del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_027676.2:n.5741del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000699272Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Nov 2, 2016)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000779243GeneDxcriteria provided, single submitter
Likely pathogenic
(Apr 17, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699272.1

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

Description

Variant summary: The c.5564delT variant creates a lost stop codon and creates a stop codon 67 amino acids downstream, resulting in an elongated protein. The variant is absent in the large ExAC control population, and has not been reported in databases or literature. Due to the absence of sufficient information, this variant has been classified as a VUS until additional evidence becomes available.

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

From GeneDx, SCV000779243.2

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

Description

This deletion of one nucleotide in BRCA1 is denoted c.5564delT at the cDNA level and p.Ile1855AsnfsX67 (I1855NfsX67) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTGA[delT]ACCC. The deletion causes a frameshift which changes an Isoleucine to an Asparagine at codon 1855 in the last exon of the gene, and results in an extension of the protein. The last 9 correct amino acids are replaced by 66 incorrect ones, disrupting a region that contains the BRCT2 domain and a region known to interact with multiple other proteins (Paul 2014, UniProt). Based on currently available evidence, we consider this deletion to be a likely pathogenic variant.

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

Last Updated: Jun 14, 2021

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