NM_032043.2(BRIP1):c.206-1G>T AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Dec 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000563712.4

Allele description [Variation Report for NM_032043.2(BRIP1):c.206-1G>T]

NM_032043.2(BRIP1):c.206-1G>T

Gene:
BRIP1:BRCA1 interacting helicase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q23.2
Genomic location:
Preferred name:
NM_032043.2(BRIP1):c.206-1G>T
HGVS:
  • NC_000017.11:g.61857232C>A
  • NG_007409.2:g.11328G>T
  • NM_032043.2:c.206-1G>T
  • LRG_300t1:c.206-1G>T
  • LRG_300:g.11328G>T
  • NC_000017.10:g.59934593C>A
Links:
dbSNP: rs1555617934
NCBI 1000 Genomes Browser:
rs1555617934
Molecular consequence:
  • NM_032043.2:c.206-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000668959Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Jan 22, 2020)
germlineclinical testing

Citation Link,

SCV001344519Color Health, Inccriteria provided, single submitter
Likely pathogenic
(Dec 22, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical 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 Ambry Genetics, SCV000668959.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.206-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 3 of the BRIP1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site. RNA studies have demonstrated that this alteration results in low level abnormal splicing and introduces a small in-frame deletion in the set of samples tested, however, functional impact is unclear at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001344519.2

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

Description

This variant causes a G to T nucleotide substitution at the -1 position of intron 3 of the BRIP1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRIP1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Likely Pathogenic.

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

Last Updated: Jun 19, 2021

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