NM_007294.3(BRCA1):c.3756_3759delGTCT (p.Ser1253Argfs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000048314.6

Allele description

NM_007294.3(BRCA1):c.3756_3759delGTCT (p.Ser1253Argfs)

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.3756_3759delGTCT (p.Ser1253Argfs)
Other names:
3874del4; 3875_3878delGTCT
HGVS:
  • NC_000017.11:g.43091772_43091775delAGAC
  • NG_005905.2:g.126209_126212delGTCT
  • NM_007294.3:c.3756_3759delGTCT
  • NM_007298.3:c.788-743_788-740delGTCT
  • NP_009225.1:p.Ser1253Argfs
  • LRG_292t1:c.3756_3759del
  • LRG_292:g.126209_126212del
  • LRG_292p1:p.Ser1253Argfs
  • NC_000017.10:g.41243789_41243792delAGAC
  • NM_007294.3:c.3756_3759del
  • NR_027676.1:n.3892_3895delGTCT
  • U14680.1:c.3756_3759delGTCT
  • U14680.1:n.3875_3878delGTCT
  • p.S1253Rfs*10
  • p.S1253RfsX10
  • p.Ser1253Argfs*10
Nucleotide change:
3875del4
Links:
Breast Cancer Information Core (BIC) (BRCA1): 3874&base_change=del TGTC; Breast Cancer Information Core (BIC) (BRCA1): 3875&base_change=del GTCT; OMIM: 113705.0014; dbSNP: rs80357868
NCBI 1000 Genomes Browser:
rs80357868
Molecular consequence:
  • NM_007294.3:c.3756_3759delGTCT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_007298.3:c.788-743_788-740delGTCT - intron variant - [Sequence Ontology: SO:0001627]
  • NR_027676.1:n.3892_3895delGTCT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000210046GeneDxcriteria provided, single submitter
Pathogenic
(Jun 15, 2017)
germlineclinical testing

Citation Link,

SCV000296325Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Pathogenic
(Apr 15, 2015)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000210046.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This deletion of four nucleotides in BRCA1 is denoted c.3756_3759delGTCT at the cDNA level and p.Ser1253ArgfsX10 (S1253RfsX10) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTCT[delGTCT]AAGA. The deletion causes a frameshift, which changes a Serine to an Arginine at codon 1253, and creates a premature stop codon at position 10 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.3756_3759delGTCT, also denoted 3875del4 using alternate nomenclature, has been published in association with breast and ovarian cancers (Castilla 1994, Zhang 2011, Alsop 2012, Gaj 2012, Ghiorzo 2012, George 2013). This variant is also a well-described pathogenic founder variant in the French-Canadian population in Quebec (Janavicius 2010). We consider this variant to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296325.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

Support Center