NM_032043.3(BRIP1):c.778A>G (p.Thr260Ala) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Dec 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000586716.12

Allele description [Variation Report for NM_032043.3(BRIP1):c.778A>G (p.Thr260Ala)]

NM_032043.3(BRIP1):c.778A>G (p.Thr260Ala)

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.778A>G (p.Thr260Ala)

Other names:

p.T260A:ACT>GCT; NP_114432.2:p.Thr260Ala

HGVS:

NC_000017.11:g.61808607T>C
NG_007409.2:g.59953A>G
NM_032043.3:c.778A>GMANE SELECT
NP_114432.2:p.Thr260Ala
NP_114432.2:p.Thr260Ala
LRG_300t1:c.778A>G
LRG_300:g.59953A>G
LRG_300p1:p.Thr260Ala
NC_000017.10:g.59885968T>C
NM_032043.2:c.778A>G
p.T260A

Protein change:

T260A

Links:

dbSNP: rs138743097

NCBI 1000 Genomes Browser:

rs138743097

Molecular consequence:

NM_032043.3:c.778A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000210869	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Dec 1, 2020)	germline	clinical testing	Citation Link,
SCV002046632	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Sep 21, 2024)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 28135145, 26976419, 26921362, 26315354, 32959997, 33471991, 28076423, 36672847, 26467025
SCV005892660	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Dec 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210869

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Dec 1, 2020)

germline

clinical testing

Citation Link,

SCV002046632

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Sep 21, 2024)

unknown

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV005892660

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Uncertain significance
(Dec 1, 2024)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]

PMID:: 26976419
PMCID:: PMC4872307

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000210869.13

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26315354, 28135145, 26976419, 26921362, 28076423, 28968953, 29641532, 32959997)

#	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, SCV002046632.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The BRIP1 c.778A>G (p.Thr260Ala) variant has been reported in the published literature in individuals with breast cancer (PMIDs: 36672847 (2022), 33471991 (2021), 32959997 (2020), 26976419 (2016), 26921362 (2016), see also LOVD (http://databases.lovd.nl/shared)) and colorectal cancer (PMID: 28135145 (2017)). It has also been observed in reportedly healthy individuals (PMIDs: 26315354 (2015), 26921362 (2016), 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared)). The frequency of this variant in the general population, 0.000039 (5/128872 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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

From CeGaT Center for Human Genetics Tuebingen, SCV005892660.3

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

Description

BRIP1: PM2

#	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

Last Updated: May 25, 2025

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