NM_007294.3(BRCA1):c.4035delA (p.Glu1346Lysfs) AND not provided

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 6, 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:: RCV000074587.7

Allele description

NM_007294.3(BRCA1):c.4035delA (p.Glu1346Lysfs)

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.4035delA (p.Glu1346Lysfs)

Other names:

Glu1346LysfsX20

HGVS:

NC_000017.11:g.43091496delT
NG_005905.2:g.126488delA
NM_007294.3:c.4035delA
NM_007298.3:c.788-464delA
NM_007300.3:c.4035delA
NP_009225.1:p.Glu1346Lysfs
NP_009231.2:p.Glu1346Lysfs
LRG_292t1:c.4035del
LRG_292:g.126488del
LRG_292p1:p.Glu1345=fs
NC_000017.10:g.41243513delT
NM_007294.3:c.4035del
NR_027676.1:n.4171delA
U14680.1:n.4154delA
p.E1346Kfs*20
p.E1346KfsX20
p.Glu1346Lysfs*20
p.Glu1346LysfsX20

Nucleotide change:

4154delA

Links:

Breast Cancer Information Core (BIC) (BRCA1): 4154&base_change=del A; OMIM: 113705.0030; dbSNP: rs80357711

NCBI 1000 Genomes Browser:

rs80357711

Molecular consequence:

NM_007294.3:c.4035delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007298.3:c.788-464delA - intron variant - [Sequence Ontology: SO:0001627]
NR_027676.1:n.4171delA - 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
SCV000108672	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 6, 2017)	germline	clinical testing	Citation Link,
SCV000296398	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Pathogenic (Apr 2, 2016)	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

SCV000108672

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 6, 2017)

germline

clinical testing

Citation Link,

SCV000296398

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Pathogenic
(Apr 2, 2016)

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, SCV000108672.13

#	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.4035delA at the cDNA level or p.Glu1346LysfsX20 (E1346KfsX20) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATGA[delA]GAAA. The deletion causes a frameshift, changing a Glutamic Acid to a Lysine at codon 1346, and creating a premature stop codon at position 20 of the new reading frame. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. BRCA1 c.4035delA, also reported as 4153delA or 4154delA using alternate nomenclature, has been observed in association with breast and/or ovarian cancer and is reported as a pathogenic founder variant in several eastern European countries (Gayther 1996, Bogdanova 2010, Janvicius 2013, Szwiec 2015, Synowiec 2016). 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, SCV000296398.3

#	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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