BRCA2 p.Arg2034Cys

Variant names:

• chr13-32340455-C-T
• rs1799954
• NM_000059.4:c.6100C>T
• BRCA2 p.Arg2034Cys

Your query was ambiguous. Multiple possible variants found:

• chr13-32340455-C-T
• chr13-32340455-CGT-TGC

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -14 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_ModerateBP6_Very_Strong

The NM_000059.4(BRCA2):c.6100C>T (p.Arg2034Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00451 (AC=7,283) in the gnomAD database across 1,613,692 control chromosomes, including 22 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.00546. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★★). Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R2034G: Uncertain_significance (ClinVar VariationId 2719621, 1 star); p.R2034H: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 52012); p.R2034L: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 1041798); p.R2034P: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 840304); p.R2034S: Conflicting_classifications_of_pathogenicity (ClinVar VariationId 479312) This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (19 hom.)
• Consequence: BRCA2 NM_000059.4 missense
• Clinical Significance: Benign reviewed by expert panel U:2 B:47 O:1
• Conservation: PhyloP100: -0.243
• Publications: 73 publications found

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) The product of this gene in involved in maintenance of genome stability. It is involved in double-strand break repair pathways during mitotic and meiotic homologous recombination and functions in protecting DNA replication forks. The encoded protein contains sites for interactions with PALB2 and EMSY and an N-terminal DNA binding domain. It also contains a RAD51 binding domain with multiple components. It has multiple BRC repeats, an alpha helix domain, oligonucleotide binding folds, and a tower-like domain. It has a nuclear localization signal and a phosphorylation site for cyclin-dependent kinase. The C-terminus of the protein can bind single-stranded and double-stranded DNA. The product of this gene interacts with multiple proteins, including RAD51. It is involved in recruiting RAD51 filaments to DNA double-strand break sites and also in cytoplasmic division. It also acts as a tumor suppressor. Mutations in this gene or decreased expression have been implicated in multiple tumor types, including breast, ovarian, pancreatic, prostate and other cancers. [provided by RefSeq, May 2026]

BRCA2 Gene-Disease associations (from GenCC):

• BRCA2-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• Fanconi anemia complementation group D1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• pancreatic cancer, susceptibility to, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Classification according to ACMG Germline Pathogenicity v2019

Specifications for BRCA2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript:

Our verdict: Benign. The variant received -14 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BP6Reputable source reports benign		ClinVar ≥3 stars benign — very strong (BP6); ClinVar submissions overwhelmingly benign (≥10 total, ≥80% B/LB, <10% P/LP) — strong (BP6, count-based); ClinVar germline classification: Benign/Likely Benign, 3 star(s). ClinVar submissions strongly and reliably favor benignity (47/49 total B/LB).
	BS2Observed in healthy adult		≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 22.; Very high cumulative gnomAD AC = 7283 (any gene).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000059.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BRCA2 NM_000059.4	MANE Select	c.6100C>T p.Arg2034Cys	missense	Exon 11 of 27	Prot: NP_000050.3 UniProt:
	BRCA2 NM_001432077.1		c.6100C>T p.Arg2034Cys	missense	Exon 11 of 27	Prot: NP_001419006.1 UniProt:
	BRCA2 NM_001406720.1		c.6100C>T p.Arg2034Cys	missense	Exon 11 of 27	Prot: NP_001393649.1 UniProt:

BRCA2 NM_000059.4

MANE Select

HGVSc / HGVSpc.6100C>Tp.Arg2034Cys

Exon rankExon 11 of 27

missense

Prot: NP_000050.3UniProt: A0A7P0T9D7P51587

BRCA2 NM_001432077.1

HGVSc / HGVSpc.6100C>Tp.Arg2034Cys

Exon rankExon 11 of 27

missense

Prot: NP_001419006.1UniProt: A0A7P0T9D7P51587

BRCA2 NM_001406720.1

HGVSc / HGVSpc.6100C>Tp.Arg2034Cys

Exon rankExon 11 of 27

missense

Prot: NP_001393649.1UniProt: A0A8V8TPZ2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BRCA2 ENST00000380152.8	TSL:5MANE Select	c.6100C>T p.Arg2034Cys	missense	Exon 11 of 27	Prot: ENSP00000369497.3 UniProt:
	BRCA2 ENST00000544455.6	TSL:1	c.6100C>T p.Arg2034Cys	missense	Exon 11 of 27	Prot: ENSP00000439902.1 UniProt:
	BRCA2 ENST00000530893.7	TSL:1	c.5731C>T p.Arg1911Cys	missense	Exon 11 of 27	Prot: ENSP00000499438.2 UniProt:

BRCA2 ENST00000380152.8

TSL:5MANE Select

HGVSc / HGVSpc.6100C>Tp.Arg2034Cys

Exon rankExon 11 of 27

missense

Prot: ENSP00000369497.3UniProt: P51587

BRCA2 ENST00000544455.6

TSL:1

HGVSc / HGVSpc.6100C>Tp.Arg2034Cys

Exon rankExon 11 of 27

missense

Prot: ENSP00000439902.1UniProt: P51587

BRCA2 ENST00000530893.7

TSL:1

HGVSc / HGVSpc.5731C>Tp.Arg1911Cys

Exon rankExon 11 of 27

missense

Prot: ENSP00000499438.2UniProt: A0A590UJI7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00338	AC:515	Hom:3	AN:152148	Cov:33
GnomAD2 exomes	AF: 0.00313	AC:785	Hom:	AN:250958	Cov:
GnomAD4 exome	AF: 0.00463	AC:6768	Hom:19	AN:1461426	Cov:46
GnomAD4 genome	AF: 0.00338	AC:515	Hom:3	AN:152266	Cov:33
TOPMed (Bravo)	AF: 0.00383	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00453	AC:3210	Hom:13	AN:708636	Cov:
Local & regional cohorts 8 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.00683	AC:16	Hom:0	AN:2342	Cov:
ESP6500 (Exome Variant Server)	AF: 0.00400	AC:52	Hom:	AN:13004	Cov:
GenomeAsia100K	AF: 0.000289	AC:1	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.000138	AC:1	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.00120	AC:2	Hom:	AN:1706	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00000800	AC:1	Hom:0	AN:121998	Cov:
Turkish Variome	AF: 0.000764	AC:5	Hom:0	AN:6542	Cov:
UK10K	AF: 0.00582	AC:44	Hom:	AN:7562	Cov:

Showing 14 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.00406 *	39	9616	0.00499 *	52	10420
BipEx(Bipolar disorder (including schizoaffective))	0.00440	125	28418	0.00447	129	28840
Epi25(Epilepsy)	0.00358	150	41958	0.00498	333	66888
SCHEMA(Schizophrenia)	0.00288	294	102008	0.00379	666	175924

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	2	13	Breast-ovarian cancer, familial, susceptibility to, 2 (15)
-	-	12	not specified (13)
-	-	8	not provided (8)
-	-	5	Hereditary breast ovarian cancer syndrome (5)
-	-	5	Hereditary cancer-predisposing syndrome (5)
-	-	2	Familial cancer of breast (2)
-	-	1	BRCA2-related cancer predisposition (1)
-	-	1	Breast and/or ovarian cancer (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	8.2
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
FuncVEP CTI	Benign	0.00097
GPN-Star LLR	N/A	-1.1
GPN-Star score	N/A	0.96
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.92	T
Mutation Taster	N/A	99/1	polymorphism
PhyloP100	Benign	-0.24
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.016	D
Sift4G	Benign	0.16	T
VESM-3B	Benign	-2.5

Showing 23 of 23 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1799954;

hg19: chr13-32914592;

COSMIC: COSV66461677;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar