NM_032043.3(BRIP1):c.1_2del (p.Met1fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 6, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000230644.6

Allele description [Variation Report for NM_032043.3(BRIP1):c.1_2del (p.Met1fs)]

NM_032043.3(BRIP1):c.1_2del (p.Met1fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.1_2del (p.Met1fs)

HGVS:

NC_000017.11:g.61861539_61861540del
NG_007409.2:g.7021_7022del
NM_032043.3:c.1_2delMANE SELECT
NP_114432.2:p.Met1fs
LRG_300:g.7021_7022del
NC_000017.10:g.59938899_59938900del
NC_000017.10:g.59938900_59938901del
NM_032043.2:c.1_2delAT
NM_032043.3:c.1_2delATMANE SELECT

Protein change:

M1fs

Links:

dbSNP: rs876661246

NCBI 1000 Genomes Browser:

rs876661246

Molecular consequence:

NM_032043.3:c.1_2del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032043.3:c.1_2del - initiator_codon_variant - [Sequence Ontology: SO:0001582]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Name:: Fanconi anemia complementation group J
Identifiers:: MONDO: MONDO:0012187; MedGen: C1836860; Orphanet: 84; OMIM: 609054

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000290967	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 6, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30322717, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000290967

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 6, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline pathogenic variants identified in women with ovarian tumors.

Carter NJ, Marshall ML, Susswein LR, Zorn KK, Hiraki S, Arvai KJ, Torene RI, McGill AK, Yackowski L, Murphy PD, Xu Z, Solomon BD, Klein RT, Hruska KS.

Gynecol Oncol. 2018 Dec;151(3):481-488. doi: 10.1016/j.ygyno.2018.09.030. Epub 2018 Oct 12.

PubMed [citation]

PMID:: 30322717

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000290967.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change deletes 2 nucleotides from exon 2 of the BRIP1 mRNA (c.1_2delAT), affecting the initiator methionine. While it is expected to result in an absent or disrupted protein product, alternate in-frame methionines at codons 4, 28, or 29, located downstream of the initiator codon could potentially rescue the translation initiation. However, functional studies have not been done to test whether these alternate methionines are utilized. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ovarian tumor (PMID:30322717). ClinVar contains an entry for this variant (Variation ID: 234832). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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