NM_007294.4(BRCA1):c.5165C>A (p.Ser1722Tyr) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 21, 2019)

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.5165C>A (p.Ser1722Tyr)]

NM_007294.4(BRCA1):c.5165C>A (p.Ser1722Tyr)

BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5165C>A (p.Ser1722Tyr)
  • NC_000017.11:g.43063361G>T
  • NG_005905.2:g.154623C>A
  • NM_007294.3:c.5165C>A
  • NM_007294.4:c.5165C>AMANE SELECT
  • NM_007297.4:c.5024C>A
  • NM_007298.3:c.1853C>A
  • NM_007299.4:c.1853C>A
  • NM_007300.4:c.5228C>A
  • NP_009225.1:p.Ser1722Tyr
  • NP_009225.1:p.Ser1722Tyr
  • NP_009228.2:p.Ser1675Tyr
  • NP_009229.2:p.Ser618Tyr
  • NP_009230.2:p.Ser618Tyr
  • NP_009231.2:p.Ser1743Tyr
  • LRG_292t1:c.5165C>A
  • LRG_292:g.154623C>A
  • LRG_292p1:p.Ser1722Tyr
  • NC_000017.10:g.41215378G>T
  • NR_027676.2:n.5342C>A
Protein change:
dbSNP: rs80357104
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007294.3:c.5165C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.5165C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.5024C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007298.3:c.1853C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007299.4:c.1853C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.5228C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.5342C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
function_uncertain_variant [Sequence Ontology: SO:0002220] - Comment(s)


Hereditary breast and ovarian cancer syndrome (HBOC)
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000759024Invitaecriteria provided, single submitter
Uncertain significance
(Nov 21, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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



Accurate classification of BRCA1 variants with saturation genome editing.

Findlay GM, Daza RM, Martin B, Zhang MD, Leith AP, Gasperini M, Janizek JD, Huang X, Starita LM, Shendure J.

Nature. 2018 Oct;562(7726):217-222. doi: 10.1038/s41586-018-0461-z. Epub 2018 Sep 12.

PubMed [citation]

Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.

Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN.

Cancer Res. 2010 Jun 15;70(12):4880-90. doi: 10.1158/0008-5472.CAN-09-4563. Epub 2010 Jun 1.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000759024.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


This sequence change replaces serine with tyrosine at codon 1722 of the BRCA1 protein (p.Ser1722Tyr). The serine residue is highly conserved and there is a large physicochemical difference between serine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 491098). This variant has been reported to have conflicting or insufficient data to determine the effect on BRCA1 protein function (PMID: 30209399). This variant disrupts the p.Ser1722 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20516115, 12496477, 25085752). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 10, 2021

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