NM_032043.3(BRIP1):c.2344A>G (p.Ile782Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 12, 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:: RCV000759709.15

Allele description [Variation Report for NM_032043.3(BRIP1):c.2344A>G (p.Ile782Val)]

NM_032043.3(BRIP1):c.2344A>G (p.Ile782Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.2

Genomic location:

Preferred name:

NM_032043.3(BRIP1):c.2344A>G (p.Ile782Val)

HGVS:

NC_000017.11:g.61743048T>C
NG_007409.2:g.125512A>G
NM_032043.3:c.2344A>GMANE SELECT
NP_114432.2:p.Ile782Val
NP_114432.2:p.Ile782Val
LRG_300t1:c.2344A>G
LRG_300:g.125512A>G
LRG_300p1:p.Ile782Val
NC_000017.10:g.59820409T>C
NM_032043.2:c.2344A>G
p.I782V

Protein change:

I782V

Links:

dbSNP: rs142806416

NCBI 1000 Genomes Browser:

rs142806416

Molecular consequence:

NM_032043.3:c.2344A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000565723	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 17, 2021)	germline	clinical testing	Citation Link,
SCV000889214	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Oct 12, 2022)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 24123366, 32659497, 31822495, 28767289, 26921362, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000565723

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 17, 2021)

germline

clinical testing

Citation Link,

SCV000889214

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Oct 12, 2022)

unknown

clinical testing

PubMed (6)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar.

Rodriguez-Flores JL, Fakhro K, Hackett NR, Salit J, Fuller J, Agosto-Perez F, Gharbiah M, Malek JA, Zirie M, Jayyousi A, Badii R, Al-Nabet Al-Marri A, Chouchane L, Stadler DJ, Mezey JG, Crystal RG.

Hum Mutat. 2014 Jan;35(1):105-16. doi: 10.1002/humu.22460. Epub 2013 Nov 10.

PubMed [citation]

PMID:: 24123366
PMCID:: PMC3908915

Association of Germline Variants in Human DNA Damage Repair Genes and Response to Adjuvant Chemotherapy in Resected Pancreatic Ductal Adenocarcinoma.

Hu H, Zhu Y, Pu N, Burkhart RA, Burns W, Laheru D, Zheng L, He J, Goggins MG, Yu J.

J Am Coll Surg. 2020 Nov;231(5):527-535.e14. doi: 10.1016/j.jamcollsurg.2020.06.019. Epub 2020 Jul 11.

PubMed [citation]

PMID:: 32659497

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000565723.4

#	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 (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with breast or pancreatic cancer (Easton 2016, Shindo 2017); Published functional studies are inconclusive: lack of cisplatin sensitivity but intermediate mitomycin C sensitivity (Moyer 2020); This variant is associated with the following publications: (PMID: 24123366, 26921362, 28767289, 27535533, 31822495)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889214.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The frequency of this variant in the general population, 0.000008 (2/251332 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals affected with breast cancer and in controls (PMID: 26921362 (2016)) as well as in individuals affected with pancreatic cancer (PMID: 28767289 (2017)). One functional study described this variant as a hypomorph due to the modest reduction in cellular growth observed after high-dose treatment with a DNA damaging agent (PMID: 31822495 (2020)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Nov 10, 2024

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