NM_000059.4(BRCA2):c.2944A>C (p.Ile982Leu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Oct 20, 2022
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:: RCV000587861.23

Allele description [Variation Report for NM_000059.4(BRCA2):c.2944A>C (p.Ile982Leu)]

NM_000059.4(BRCA2):c.2944A>C (p.Ile982Leu)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2944A>C (p.Ile982Leu)

Other names:

p.I982L:ATA>CTA

HGVS:

NC_000013.11:g.32337299A>C
NG_012772.3:g.26820A>C
NM_000059.4:c.2944A>CMANE SELECT
NP_000050.2:p.Ile982Leu
NP_000050.3:p.Ile982Leu
LRG_293t1:c.2944A>C
LRG_293:g.26820A>C
LRG_293p1:p.Ile982Leu
NC_000013.10:g.32911436A>C
NM_000059.3:c.2944A>C
U43746.1:n.3172A>C
p.I982L

Protein change:

I982L

Links:

dbSNP: rs28897717

NCBI 1000 Genomes Browser:

rs28897717

Molecular consequence:

NM_000059.4:c.2944A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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NBAS NBAS subunit of NRZ tethering complex [Homo sapiens]
NBAS NBAS subunit of NRZ tethering complex [Homo sapiens]
Gene ID:51594

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000225161	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Apr 28, 2015)	germline	clinical testing	Citation Link,
SCV000600535	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Oct 20, 2022)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 28873162, 30254663, 33471991, 32438681, 34597585, 31159747, 16905680, 31131967, 26467025
SCV000694651	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Aug 24, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16905680, 22476429, 26689913 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000778657	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Benign (May 1, 2024)	unknown	clinical testing

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Summary from all submissions

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

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A, Pradhan N, Arnold A, Walsh MF, Li Y, Balakrishnan AR, Syed A, Prasad M, Nafa K, Carlo MI, Cadoo KA, Sheehan M, Fleischut MH, Salo-Mullen E, Trottier M, Lipkin SM, Lincoln A, et al.

JAMA. 2017 Sep 5;318(9):825-835. doi: 10.1001/jama.2017.11137. Erratum in: JAMA. 2018 Dec 11;320(22):2381. doi: 10.1001/jama.2018.17511.

PubMed [citation]

PMID:: 28873162
PMCID:: PMC5611881

Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?

Zuntini R, Ferrari S, Bonora E, Buscherini F, Bertonazzi B, Grippa M, Godino L, Miccoli S, Turchetti D.

Front Genet. 2018;9:378. doi: 10.3389/fgene.2018.00378.

PubMed [citation]

PMID:: 30254663
PMCID:: PMC6141711

See all PubMed Citations (11)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000225161.5

#	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	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600535.3

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

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694651.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The BRCA2 c.2944A>C (p.Ile982Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC in 5/120330 control chromosomes at a frequency of 0.0000416, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in the literature in an affected individual, without strong evidence for causality. Three clinical diagnostic laboratories classified this variant as uncertain significance, and one other lab classified it as benign, all without evidence for independent evaluaiton. UMD and BIC databases cite this variant in three individuals as co-occurring with pathogenic variants BRCA1 c.4327C>T (p.Arg1443X), BRCA1 c.4964_4982del (p.Ser956=fs), and BRCA2 c.7638-7647del (p.Lys257X), respectively, supporting the non-pathogenic role of this variant. Taken together, this variant is classified as likely benign.

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV000778657.2

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

Description

BS1_sup, BS4, BP1_strong, BP5_mod

#	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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