NM_007294.4(BRCA1):c.2123C>A (p.Ser708Tyr) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jun 26, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_007294.4(BRCA1):c.2123C>A (p.Ser708Tyr)]

NM_007294.4(BRCA1):c.2123C>A (p.Ser708Tyr)

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.2123C>A (p.Ser708Tyr)
  • NC_000017.11:g.43093408G>T
  • NG_005905.2:g.124576C>A
  • NM_007294.3:c.2123C>A
  • NM_007294.4:c.2123C>AMANE SELECT
  • NM_007297.4:c.1982C>A
  • NM_007298.3:c.787+1336C>A
  • NM_007299.4:c.787+1336C>A
  • NM_007300.4:c.2123C>A
  • NP_009225.1:p.Ser708Tyr
  • NP_009225.1:p.Ser708Tyr
  • NP_009228.2:p.Ser661Tyr
  • NP_009231.2:p.Ser708Tyr
  • LRG_292t1:c.2123C>A
  • LRG_292:g.124576C>A
  • LRG_292p1:p.Ser708Tyr
  • NC_000017.10:g.41245425G>T
  • NM_007294.4:c.2123C>A
  • NR_027676.2:n.2300C>A
  • U14680.1:n.2242C>A
  • p.S708Y
Nucleotide change:
Protein change:
dbSNP: rs80357182
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007298.3:c.787+1336C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+1336C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.2123C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.2123C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.1982C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.2123C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.2300C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000329124GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 26, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000329124.5

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


This variant is denoted BRCA1 c.2123C>A at the cDNA level, p.Ser708Tyr (S708Y) at the protein level, and results in the change of a Serine to a Tyrosine (TCT>TAT). Using alternate nomenclature, this variant would be defined as BRCA1 2242C>A. This variant has been observed in individuals with breast cancer, and displayed homology directed repair activity comparable to wild-type in an in vitro functional study (Lu 2015, Azzolini 2016). BRCA1 Ser708Tyr was observed at an allele frequency of 0.04% (12/30,780) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the DNA binding domain and the RAD50 and STAT1 binding domains (Zhong 1999, Ouchi 2000, Narod 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Ser708Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance.

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

Last Updated: Sep 23, 2021

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