rs276174816

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000059.4(BRCA2):c.1909+21_1909+22delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,106,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BRCA2
NM_000059.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.591

Publications

14 publications found

Variant links:

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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

BRCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP6

Variant 13-32333398-CTT-C is Benign according to our data. Variant chr13-32333398-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 2691924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	NM_000059.4	MANE Select	c.1909+21_1909+22delTT	intron	N/A	NP_000050.3	A0A7P0T9D7
BRCA2	NM_001432077.1		c.1909+21_1909+22delTT	intron	N/A	NP_001419006.1	A0A7P0T9D7
BRCA2	NM_001406720.1		c.1909+21_1909+22delTT	intron	N/A	NP_001393649.1	A0A8V8TPZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	ENST00000380152.8	TSL:5 MANE Select	c.1909+12_1909+13delTT	intron	N/A	ENSP00000369497.3	P51587
BRCA2	ENST00000544455.6	TSL:1	c.1909+12_1909+13delTT	intron	N/A	ENSP00000439902.1	P51587
BRCA2	ENST00000530893.7	TSL:1	c.1540+12_1540+13delTT	intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146156

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000276

AC:

AN:

79632

AF XY:

0.000329

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000759

Gnomad ASJ exome

AF:

0.000342

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1106636

Hom.:

AF XY:

0.0000400

AC XY:

AN XY:

549982

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000119

AC:

AN:

25232

American (AMR)

AF:

0.000208

AC:

AN:

33686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19520

East Asian (EAS)

AF:

0.00

AC:

AN:

29620

South Asian (SAS)

AF:

0.0000632

AC:

AN:

63330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4568

European-Non Finnish (NFE)

AF:

0.0000177

AC:

AN:

845932

Other (OTH)

AF:

0.0000659

AC:

AN:

45504

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

146210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71070

African (AFR)

AF:

0.00

AC:

AN:

40062

American (AMR)

AF:

0.00

AC:

AN:

14614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

5012

South Asian (SAS)

AF:

0.00

AC:

AN:

4638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66056

Other (OTH)

AF:

0.00

AC:

AN:

2016

Alfa

AF:

0.00113

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary breast ovarian cancer syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over