NM_032043.3(BRIP1):c.1425_1429del (p.Leu475fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 1, 2021
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:: RCV000657382.4

Allele description [Variation Report for NM_032043.3(BRIP1):c.1425_1429del (p.Leu475fs)]

NM_032043.3(BRIP1):c.1425_1429del (p.Leu475fs)

Gene:

BRIP1:BRCA1 interacting DNA helicase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.1425_1429del (p.Leu475fs)

HGVS:

NC_000017.11:g.61793644_61793648del
NG_007409.2:g.74915_74919del
NM_032043.3:c.1425_1429delMANE SELECT
NP_114432.2:p.Leu475fs
LRG_300:g.74915_74919del
NC_000017.10:g.59871002_59871006del
NC_000017.10:g.59871005_59871009del
NM_032043.2:c.1425_1429delAACTT
NM_032043.3:c.1425_1429del

Links:

dbSNP: rs768736851

NCBI 1000 Genomes Browser:

rs768736851

Molecular consequence:

NM_032043.3:c.1425_1429del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779115	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Sep 8, 2017)	germline	clinical testing	Citation Link,
SCV001480053	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779115

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Sep 8, 2017)

germline

clinical testing

Citation Link,

SCV001480053

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

germline

clinical testing

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

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	1	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 GeneDx, SCV000779115.1

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

Description

This deletion of five nucleotides in BRIP1 is denoted c.1425_1429delAACTT at the cDNA level and p.Leu475PhefsX34 (L475FfsX34) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TCTT[delAACTT]TACA. The deletion causes a frameshift, which changes a Leucine to a Phenylalanine at codon 475 and creates a premature stop codon at position 34 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available evidence, we consider this deletion to be a likely pathogenic variant.

#	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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001480053.1

#	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	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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