This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.162CAA[1] (p.Asn56del)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(15)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(1); Likely benign(9)
Uncertain significance(1); Benign(1); Likely benign(9)
15
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.162CAA[1] (p.Asn56del)
Variation ID: 96767 Accession: VCV000096767.57
- Type and length
-
Microsatellite, 3 bp
- Location
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Cytogenetic: 13q13.1 13: 32893306-32893308 (GRCh37) [ NCBI UCSC ] 13: 32319169-32319171 (GRCh38) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Oct 20, 2024 Mar 14, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.162CAA[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Asn56del inframe deletion NM_000059.4:c.165_167delCAA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000059.3:c.165_167delCAA NC_000013.11:g.32319171CAA[1] NC_000013.10:g.32893308CAA[1] NG_012772.3:g.8692CAA[1] NG_017006.2:g.1190GTT[1] LRG_293:g.8692CAA[1] LRG_293t1:c.165_167del U43746.1:n.393_395delCAA - Protein change
- N56del
- Other names
-
N55del
393del3
- Canonical SPDI
- NC_000013.11:32319168:AACAACAA:AACAA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18985 | 19144 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (3) |
no assertion criteria provided
|
Mar 2, 2020 | RCV000082888.11 | |
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 14, 2024 | RCV000160245.13 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 23, 2021 | RCV000164468.11 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 7, 2024 | RCV000205603.18 | |
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 1, 2023 | RCV001091525.24 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 29, 2022 | RCV003492433.1 | |
| Likely benign (1) |
no assertion criteria provided
|
Nov 3, 2022 | RCV004542799.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely benign
(May 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002047315.2
First in ClinVar: Jan 01, 2022 Last updated: Jan 06, 2024 |
|
|
|
Likely benign
(Jul 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000215112.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Likely benign
(Mar 14, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916838.6
First in ClinVar: Jun 02, 2019 Last updated: Jun 29, 2024 |
Comment:
Variant summary: BRCA2 c.165_167delCAA (p.Asn56del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele … (more)
Variant summary: BRCA2 c.165_167delCAA (p.Asn56del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2e-05 in 251382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance.c.165_167delCAA variant has been reported in several affected individuals via publications without strong evidence for causality (example: de Juan Jimenez_2011). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variants have been reported (BIC) and observed internally (BRCA2 c.1929_1929delG, p.Arg645fs; BRCA1 c.5177_5180delGAAA, p.Arg1726fs; BRCA2 c.3744_3747delTGAG, p.Ser1248fs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed variant was complementation positive with a 70% HDR capacity and an 84% cisplatin sensitivity (Mesman_2018). The following publications have been ascertained in the context of this evaluation (PMID: 19941162, 20167696, 21147080, 29988080). ClinVar contains an entry for this variant (Variation ID: 96767). Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
|
Likely benign
(Apr 24, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002069158.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
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Likely benign
(Jun 23, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002533249.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
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Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004027390.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
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Uncertain significance
(Jul 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004240293.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
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Likely benign
(Jan 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000261016.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
|
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Benign
(Dec 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683436.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
|
Likely benign
(Sep 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210657.8
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 29988080)
|
|
|
Likely benign
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247633.19
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
BRCA2: PM4:Supporting, BP4, BS3:Supporting
Number of individuals with the variant: 2
|
|
|
Uncertain significance
(Feb 20, 2004)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146283.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 2
Observation 2:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European
|
|
|
Benign
(Jan 28, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000114962.4
First in ClinVar: Feb 09, 2014 Last updated: May 27, 2015 |
|
|
|
Likely benign
(Mar 02, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV004243648.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
Likely benign
(Nov 03, 2022)
|
no assertion criteria provided
Method: clinical testing
|
BRCA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004757482.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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| click to load more click to collapse | |||||
Comment:
Comment:
Variant summary: BRCA2 c.165_167delCAA (p.Asn56del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2e-05 in 251382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance.c.165_167delCAA variant has been reported in several affected individuals via publications without strong evidence for causality (example: de Juan Jimenez_2011). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variants have been reported (BIC) and observed internally (BRCA2 c.1929_1929delG, p.Arg645fs; BRCA1 c.5177_5180delGAAA, p.Arg1726fs; BRCA2 c.3744_3747delTGAG, p.Ser1248fs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed variant was complementation positive with a 70% HDR capacity and an 84% cisplatin sensitivity (Mesman_2018). The following publications have been ascertained in the context of this evaluation (PMID: 19941162, 20167696, 21147080, 29988080). ClinVar contains an entry for this variant (Variation ID: 96767). Based on the evidence outlined above, the variant was classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 29988080)
Comment:
BRCA2: PM4:Supporting, BP4, BS3:Supporting
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Variant summary: BRCA2 c.165_167delCAA (p.Asn56del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2e-05 in 251382 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance.c.165_167delCAA variant has been reported in several affected individuals via publications without strong evidence for causality (example: de Juan Jimenez_2011). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variants have been reported (BIC) and observed internally (BRCA2 c.1929_1929delG, p.Arg645fs; BRCA1 c.5177_5180delGAAA, p.Arg1726fs; BRCA2 c.3744_3747delTGAG, p.Ser1248fs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed variant was complementation positive with a 70% HDR capacity and an 84% cisplatin sensitivity (Mesman_2018). The following publications have been ascertained in the context of this evaluation (PMID: 19941162, 20167696, 21147080, 29988080). ClinVar contains an entry for this variant (Variation ID: 96767). Based on the evidence outlined above, the variant was classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 29988080)
Comment:
BRCA2: PM4:Supporting, BP4, BS3:Supporting
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical, splicing, and functional analysis to classify BRCA2 exon 3 variants: Application of a points-based ACMG/AMP approach. | Thomassen M | Human mutation | 2022 | PMID: 35979650 |
| The functional impact of variants of uncertain significance in BRCA2. | Mesman RLS | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29988080 |
| Advantage of high-resolution melting curve analysis over conformation-sensitive gel electrophoresis for mutational screening of BRCA1 and BRCA2 genes. | de Juan Jiménez I | Clinica chimica acta; international journal of clinical chemistry | 2011 | PMID: 21147080 |
| Interlaboratory diagnostic validation of conformation-sensitive capillary electrophoresis for mutation scanning. | Mattocks CJ | Clinical chemistry | 2010 | PMID: 20167696 |
| High-throughput resequencing in the diagnosis of BRCA1/2 mutations using oligonucleotide resequencing microarrays. | Schroeder C | Breast cancer research and treatment | 2010 | PMID: 19941162 |
Text-mined citations for rs11571587 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.