NM_000059.4(BRCA2):c.7762_7764delinsTT (p.Ile2588fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 6, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000254816.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.7762_7764delinsTT (p.Ile2588fs)]

NM_000059.4(BRCA2):c.7762_7764delinsTT (p.Ile2588fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.7762_7764delinsTT (p.Ile2588fs)

Other names:

7990_7992delATAinsTT

HGVS:

NC_000013.11:g.32357886_32357888delinsTT
NG_012772.3:g.47407_47409delinsTT
NM_000059.4:c.7762_7764delinsTTMANE SELECT
NP_000050.3:p.Ile2588fs
LRG_293:g.47407_47409delinsTT
NC_000013.10:g.32932023_32932025delinsTT
NM_000059.3:c.7762_7764delATAinsTT
NM_000059.4:c.7762_7764delinsTT
p.Ile2588PhefsX60

Protein change:

I2588fs

Links:

dbSNP: rs483353072

NCBI 1000 Genomes Browser:

rs483353072

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000296731	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Nov 6, 2020)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 30274973, 12960223, 18824701, 18703817, 22706548, 20104584, 26467025, 26295337
SCV000322114	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 11, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000296731

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Nov 6, 2020)

unknown

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV000322114

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 11, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

Bannon SA, Montiel MF, Goldstein JB, Dong W, Mork ME, Borras E, Hasanov M, Varadhachary GR, Maitra A, Katz MH, Feng L, Futreal A, Fogelman DR, Vilar E, McAllister F.

Cancer Prev Res (Phila). 2018 Nov;11(11):679-686. doi: 10.1158/1940-6207.CAPR-18-0014. Epub 2018 Oct 1.

PubMed [citation]

PMID:: 30274973
PMCID:: PMC6343472

Sensitivity of BRCA1/2 mutation testing in 466 breast/ovarian cancer families.

Evans DG, Bulman M, Young K, Gokhale D, Lalloo F.

J Med Genet. 2003 Sep;40(9):e107. No abstract available.

PubMed [citation]

PMID:: 12960223
PMCID:: PMC1735589

See all PubMed Citations (8)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296731.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. In the published literature, this variant has been reported in individuals and families with hereditary breast and/or ovarian cancer (PMIDs: 12960223 (2003), 18703817 (2008), 18824701 (2008), 20104584 (2010)) and pancreatic cancer (PMID: 30274973 (2018)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

#	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 GeneDx, SCV000322114.8

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 7990del3ins2 or 7990delATAinsTT; This variant is associated with the following publications: (PMID: 25685387, 27181684, 12960223, 20104584, 24307375, 23242139, 22706548, 18703817, 15131399, 26295337, 30274973, 31447099)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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