NM_007294.4(BRCA1):c.5123C>T (p.Ala1708Val) AND Hereditary cancer-predisposing syndrome

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

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 26, 2020
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:: RCV000131166.9

Allele description

NM_007294.4(BRCA1):c.5123C>T (p.Ala1708Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.4(BRCA1):c.5123C>T (p.Ala1708Val)

Other names:

p.A1708V:GCG>GTG

HGVS:

NC_000017.11:g.43063903G>A
NG_005905.2:g.154081C>T
NM_007294.3:c.5123C>T
NM_007294.4:c.5123C>TMANE SELECT
NM_007297.4:c.4982C>T
NM_007298.3:c.1811C>T
NM_007299.4:c.1811C>T
NM_007300.4:c.5186C>T
NP_009225.1:p.Ala1708Val
NP_009225.1:p.Ala1708Val
NP_009228.2:p.Ala1661Val
NP_009229.2:p.Ala604Val
NP_009230.2:p.Ala604Val
NP_009231.2:p.Ala1729Val
LRG_292t1:c.5123C>T
LRG_292:g.154081C>T
LRG_292p1:p.Ala1708Val
NC_000017.10:g.41215920G>A
NM_007294.2:c.5123C>T
NR_027676.2:n.5300C>T
p.A1708V

Nucleotide change:

5242C>T

Protein change:

A1661V

Links:

dbSNP: rs28897696

Molecular consequence:

NM_007294.3:c.5123C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007294.4:c.5123C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007297.4:c.4982C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007298.3:c.1811C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007299.4:c.1811C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007300.4:c.5186C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_027676.2:n.5300C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186111	Ambry Genetics	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (2/2020))	Uncertain significance (Feb 26, 2020)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 19404736, 22034289, 25637381, 26689913, 27495310, 28024868, 30263132, 30458859, 30765603 Citation Link,
SCV000688538	Color Health, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 12, 2019)	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

SCV000186111

Ambry Genetics

criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (2/2020))

Uncertain significance
(Feb 26, 2020)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link,

SCV000688538

Color Health, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 12, 2019)

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

Citations

PubMed

The c.5242C>A BRCA1 missense variant induces exon skipping by increasing splicing repressors binding.

Millevoi S, Bernat S, Telly D, Fouque F, Gladieff L, Favre G, Vagner S, Toulas C.

Breast Cancer Res Treat. 2010 Apr;120(2):391-9. doi: 10.1007/s10549-009-0392-3. Epub 2009 Apr 30.

PubMed [citation]

PMID:: 19404736

High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients.

Fackenthal JD, Zhang J, Zhang B, Zheng Y, Hagos F, Burrill DR, Niu Q, Huo D, Sveen WE, Ogundiran T, Adebamowo C, Odetunde A, Falusi AG, Olopade OI.

Int J Cancer. 2012 Sep 1;131(5):1114-23. doi: 10.1002/ijc.27326. Epub 2012 Jan 27.

PubMed [citation]

PMID:: 22034289

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000186111.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (9)

Description

The p.A1708V variant (also known as c.5123C>T), located in coding exon 16 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5123. The alanine at codon 1708 is replaced by valine, an amino acid with similar properties. This alteration, referred to as 5242C>T in some literature, impacts the functionally important BRCT domain and has been associated with reduced/partial BRCA1 function, suggesting that p.A1708V may act as a low or moderate disease risk allele (Lu C et al. Nat Commun. 2015 Dec;6:10086; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Lovelock PK et al. Breast Cancer Res. 2007;9:R82). This alteration has been classified as having uncertain clinical significance by multifactorial analysis, which integrates which integrates the following lines of evidence to produce a quantitative likelihood of pathogenicity: in silico prediction models, segregation with disease, tumor characteristics, and mutation co-occurrence (Easton DF et al. Am. J. Hum. Genet. 2007 Nov;81:873-83; Lindor NM et al. Hum. Mutat. 2012 Jan;33:8-21; Vallee MP et al. Hum. Mutat. 2012 Jan;33:22-8). Based on one functional study, using saturation genome editing, this alteration does not affect the BRCA1 protein (Findlay GM et al. Nature. 2018 10;562:217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence conflicting at this time, the clinical significance of this alteration remains unclear.

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

From Color Health, Inc, SCV000688538.3

#	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: Jun 15, 2021

ClinVar

Relating variation to medicine