NM_007294.3(BRCA1):c.5277+1G>A AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 5, 2018
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:: RCV000235135.3

Allele description

NM_007294.3(BRCA1):c.5277+1G>A

Gene:

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.3(BRCA1):c.5277+1G>A

Other names:

IVS19+1 G>A

HGVS:

NC_000017.11:g.43057051C>T
NG_005905.2:g.160933G>A
NM_007294.3:c.5277+1G>A
NM_007299.3:c.1965+1G>A
NM_007300.3:c.5340+1G>A
LRG_292t1:c.5277+1G>A
LRG_292:g.160933G>A
NC_000017.10:g.41209068C>T
U14680.1:n.5396+1G>A

Nucleotide change:

IVS20+1G>A

Links:

BRCA1-HCI: BRCA1_00146; Breast Cancer Information Core (BIC) (BRCA1): 5396+1&base_change=G to A; dbSNP: rs80358150

Molecular consequence:

NM_007294.3:c.5277+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000108686	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Mar 5, 2018)	germline	clinical testing	Citation Link,
SCV000296332	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Pathogenic (Jul 1, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26467025, 26295337

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000108686

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Mar 5, 2018)

germline

clinical testing

Citation Link,

SCV000296332

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Pathogenic
(Jul 1, 2015)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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	germline	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

Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory.

Strom CM, Rivera S, Elzinga C, Angeloni T, Rosenthal SH, Goos-Root D, Siaw M, Platt J, Braastadt C, Cheng L, Ross D, Sun W.

PLoS One. 2015;10(8):e0136419. doi: 10.1371/journal.pone.0136419.

PubMed [citation]

PMID:: 26295337
PMCID:: PMC4546651

Details of each submission

From GeneDx, SCV000108686.13

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

Description

This pathogenic variant is denoted BRCA1 c.5277+1G>A or IVS19+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 19 of the BRCA1 gene. The variant destroys a canonical splice donor site and has been proven through functional studies to cause exonic skipping, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product (Tesoriero 2005, Sanz 2010, Steffensen 2014). This variant, also known as BRCA1 5396+1G>A or IVS20+1G>A using alternate nomenclature, has been reported in individuals with early-onset or familial breast and/or ovarian cancer (de la Hoya 2001, Diez 2003, van Harssel 2010, Lara 2012). Based on the current evidence, we consider this variant 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, SCV000296332.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

Last Updated: Mar 31, 2019

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