ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.17_18del (p.Lys6fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.17_18del (p.Lys6fs)
Variation ID: 51198 Accession: VCV000051198.14
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 13q13.1 13: 32316476-32316477 (GRCh38) [ NCBI UCSC ] 13: 32890613-32890614 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 20, 2024 Sep 8, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.17_18del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Lys6fs frameshift NM_000059.3:c.17_18delAA NC_000013.11:g.32316477_32316478del NC_000013.10:g.32890614_32890615del NG_012772.3:g.5998_5999del NG_017006.2:g.3887_3888del LRG_293:g.5998_5999del U43746.1:n.245_246delAA - Protein change
- Other names
- 245delAA
- Canonical SPDI
- NC_000013.11:32316475:AAA:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18445 | 18602 |
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. |
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Pathogenic (4) |
reviewed by expert panel
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Sep 8, 2016 | RCV000113025.14 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 17, 2015 | RCV000486492.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 22, 2022 | RCV001012799.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 6, 2022 | RCV001852922.11 |
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. |
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Pathogenic
(Sep 08, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300283.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326593.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Likely pathogenic
(Dec 17, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000569030.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
This deletion of 2 nucleotides in BRCA2 is denoted c.17_18delAA at the cDNA level and p.Lys6ArgfsX7(K6RfsX7) at the protein level. Using alternate nomenclature, this variant … (more)
This deletion of 2 nucleotides in BRCA2 is denoted c.17_18delAA at the cDNA level and p.Lys6ArgfsX7(K6RfsX7) at the protein level. Using alternate nomenclature, this variant may be defined as BRCA2 245_246delAA. The normal sequence, with the bases that are deleted in braces, is TCCA[AA]GAGA. The deletion causes a frameshift, which changes a Lysine to an Arginine at codon 6, and creates a premature stop codon at position 7 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. (less)
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Pathogenic
(Nov 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001173299.4
First in ClinVar: Mar 16, 2020 Last updated: Apr 15, 2023 |
Comment:
The c.17_18delAA pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 17 to … (more)
The c.17_18delAA pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 17 to 18, causing a translational frameshift with a predicted alternate stop codon (p.K6Rfs*7). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Sep 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002232098.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 51198). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 51198). This variant is also known as c.16_17del. This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 29752822). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys6Argfs*7) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). (less)
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Pathogenic
(Jun 22, 1999)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146019.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 2:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European
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Pathogenic
(Dec 27, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000189296.1
First in ClinVar: Sep 27, 2014 Last updated: Sep 27, 2014 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Text-mined citations for rs80359298 ...
HelpRecord last updated Apr 15, 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.