NM_000059.4(BRCA2):c.7617+1G>C AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 23, 2019
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:: RCV000235926.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.7617+1G>C]

NM_000059.4(BRCA2):c.7617+1G>C

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.7617+1G>C

HGVS:

NC_000013.11:g.32356610G>C
NG_012772.3:g.46131G>C
NM_000059.4:c.7617+1G>CMANE SELECT
NM_001406719.1:c.7521+1G>C
NM_001406720.1:c.7617+1G>C
NM_001406721.1:c.2685+1G>C
NM_001406722.1:c.1200+1G>C
LRG_293t1:c.7617+1G>C
LRG_293:g.46131G>C
NC_000013.10:g.32930747G>C
NM_000059.3:c.7617+1G>C

Links:

dbSNP: rs397507922

NCBI 1000 Genomes Browser:

rs397507922

Molecular consequence:

NM_000059.4:c.7617+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.7521+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.7617+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.2685+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.1200+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Homo sapiens BBP-like protein 1 (BLP1), transcript variant 1, mRNA
Homo sapiens BBP-like protein 1 (BLP1), transcript variant 1, mRNA
gi|17865796|ref|NM_078473.1|

Nucleotide
AGENCOURT_86398485 NICHD_XGC_panc Xenopus laevis cDNA clone IMAGE:8734850 5', mR...
AGENCOURT_86398485 NICHD_XGC_panc Xenopus laevis cDNA clone IMAGE:8734850 5', mRNA sequence
gi|111582303|gnl|dbEST|40924148|gb| 883.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293723	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 16, 2015)	germline	clinical testing	Citation Link,
SCV001133909	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jul 23, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293723

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 16, 2015)

germline

clinical testing

Citation Link,

SCV001133909

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jul 23, 2019)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000293723.10

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

Description

This variant is denoted BRCA2 c.7617+1G>C or IVS15+1G>C and consists of a G>C nucleotide substitution at the +1 position of intron 15 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 7845+1G>C. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature. However, c.7617+1G>A and c.7617+1G>T have both been observed in individuals with familial breast and ovarian cancer and found to cause exon 15 skipping when functionally interrogated (van der Hout 2006, Thomassen 2011, Houdayer 2012, de Garibay 2014). Based on the current evidence, we consider BRCA2 c.7617+1G>C to be pathogenic.

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001133909.3

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

Description

The BRCA2 c.7617+1G>C variant disrupts a canonical splice-donor site and interferes with normal BRCA2 mRNA splicing. This variant has not been reported in individuals with BRCA2-related conditions in the published literature. 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

Last Updated: Sep 29, 2024

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