NM_007294.3(BRCA1):c.1961delA (p.Lys654Serfs) AND not provided

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

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 3, 2017
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:: RCV000236783.5

Allele description

NM_007294.3(BRCA1):c.1961delA (p.Lys654Serfs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.3(BRCA1):c.1961delA (p.Lys654Serfs)

HGVS:

NC_000017.11:g.43093570delT
NG_005905.2:g.124414delA
NM_007294.3:c.1961delA
NM_007298.3:c.787+1174delA
NM_007300.3:c.1961delA
NP_009225.1:p.Lys654Serfs
NP_009231.2:p.Lys654Serfs
LRG_292t1:c.1961_1961del
LRG_292:g.124414del
LRG_292p1:p.Lys654Serfs
NC_000017.10:g.41245587delT
NM_007294.3:c.1961_1961delA
NM_007294.3:c.1961del
NR_027676.1:n.2097delA
U14680.1:n.2080delA
p.K654SFS*47
p.Lys654Serfs*47
p.Lys654SerfsX47

Nucleotide change:

2080delA

Links:

Breast Cancer Information Core (BIC) (BRCA1): 2080&base_change=del A; dbSNP: rs80357522

NCBI 1000 Genomes Browser:

rs80357522

Molecular consequence:

NM_007294.3:c.1961delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007298.3:c.787+1174delA - intron variant - [Sequence Ontology: SO:0001627]
NR_027676.1:n.2097delA - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000292510	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 3, 2017)	germline	clinical testing	Citation Link,
SCV000296329	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Pathogenic (Apr 24, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26467025, 26295337
SCV000806905	PreventionGenetics,PreventionGenetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 16, 2017)	germline	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

SCV000292510

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 3, 2017)

germline

clinical testing

Citation Link,

SCV000296329

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Pathogenic
(Apr 24, 2015)

germline

clinical testing

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

SCV000806905

PreventionGenetics,PreventionGenetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 16, 2017)

germline

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	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

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000292510.9

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

Description

This deletion of one nucleotide in BRCA1 is denoted c.1961delA at the cDNA level and p.Lys654SerfsX47 (K654SfsX47) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAAAAAA[delA]GTAC. The deletion causes a frameshift, which changes a Lysine to a Serine at codon 654, and creates a premature stop codon at position 47 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.1961delA, previously denoted as 2073delA and 2080delA using alternate nomenclature, has been reported in individuals with female and male breast cancer, ovarian cancer (Gayther 1995, Risch 2001, Diez 2003, Abugattas 2015, Couch 2015, de Juan 2015, Kang 2015) and as a recurrent variant in individuals of Spanish descent with breast and/or ovarian cancer (de Juan Jimenez 2013). 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, SCV000296329.3

#	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

From PreventionGenetics,PreventionGenetics, SCV000806905.1

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

#	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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