NM_032043.3(BRIP1):c.1899C>G (p.Ile633Met) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 21, 2022
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:: RCV001171799.20

Allele description [Variation Report for NM_032043.3(BRIP1):c.1899C>G (p.Ile633Met)]

NM_032043.3(BRIP1):c.1899C>G (p.Ile633Met)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.1899C>G (p.Ile633Met)

HGVS:

NC_000017.11:g.61780297G>C
NG_007409.2:g.88263C>G
NM_032043.3:c.1899C>GMANE SELECT
NP_114432.2:p.Ile633Met
NP_114432.2:p.Ile633Met
LRG_300t1:c.1899C>G
LRG_300:g.88263C>G
LRG_300p1:p.Ile633Met
NC_000017.10:g.59857658G>C
NM_032043.2:c.1899C>G

Protein change:

I633M

Links:

dbSNP: rs28997572

NCBI 1000 Genomes Browser:

rs28997572

Molecular consequence:

NM_032043.3:c.1899C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001334659	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Feb 1, 2020)	germline	clinical testing	Citation Link,
SCV001552733	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing
SCV002769984	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 21, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001334659

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Feb 1, 2020)

germline

clinical testing

Citation Link,

SCV001552733

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

SCV002769984

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 21, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001334659.19

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

#	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		1	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552733.1

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

Description

The BRIP1 p.Ile633Met variant was identified in 2 of 7448 proband chromosomes (frequency: 0.00023) from individuals or families with hereditary breast and ovarian cancer and was present in 1 of 6862 control chromosomes (frequency: 0.0001) from healthy individuals (Ramus 2015, Tung 2016). The variant was also identified in dbSNP (ID: rs28997572) as â€šÃ„ÃºWith Uncertain significance alleleâ€šÃ„Ã¹, ClinVar (as uncertain significance by Ambry Genetics, Invitae, and Color Genomics), Clinvitae, and Zhejiang University Database. The variant was not identified in the Cosmic or MutDB database. The variant was identified in the Exome Aggregation Consortium (August 8th 2016) control database in 1 of 121336 chromosomes at a frequency of 0.000008 in the following populations: Latino in 1 of 11578 chromosomes (freq: 0.000086), but not observed in the African, East Asian, European (Finnish), European (Non-Finnish), Other, or South Asian populations. The variant was not identified in the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (Feb 27, 2017). The p.Ile633 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

From GeneDx, SCV002769984.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer, ovarian cancer, or melanoma, but also in unaffected controls (Ramus et al., 2015; Easton et al., 2016; Tung et al., 2016; Pritchard et al., 2018; Dorling et al., 2021); This variant is associated with the following publications: (PMID: 26315354, 26976419, 29641532, 26921362, 33471991)

#	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

Last Updated: Apr 15, 2024

ClinVar

Relating variation to medicine