NM_000059.3(BRCA2):c.1054T>C (p.Tyr352His) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000485522.3

Allele description [Variation Report for NM_000059.3(BRCA2):c.1054T>C (p.Tyr352His)]

NM_000059.3(BRCA2):c.1054T>C (p.Tyr352His)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.1054T>C (p.Tyr352His)
HGVS:
  • NC_000013.11:g.32332532T>C
  • NG_012772.3:g.22053T>C
  • NM_000059.3:c.1054T>C
  • NP_000050.2:p.Tyr352His
  • LRG_293t1:c.1054T>C
  • LRG_293:g.22053T>C
  • LRG_293p1:p.Tyr352His
  • NC_000013.10:g.32906669T>C
  • p.Y352H
Protein change:
Y352H
Links:
dbSNP: rs542343726
NCBI 1000 Genomes Browser:
rs542343726
Molecular consequence:
  • NM_000059.3:c.1054T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000569857GeneDxcriteria provided, single submitter
Likely benign
(Jul 21, 2017)
germlineclinical testing

Citation Link,

SCV001426859Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 17, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

BRCA1 and BRCA2 mutations in breast cancer patients from Venezuela.

Lara K, Consigliere N, PĂ©rez J, Porco A.

Biol Res. 2012;45(2):117-30. doi: 10.4067/S0716-97602012000200003.

PubMed [citation]
PMID:
23096355

Details of each submission

From GeneDx, SCV000569857.3

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001426859.1

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

Description

Variant summary: BRCA2 c.1054T>C (p.Tyr352His) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 247576 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1054T>C has been reported in the literature in at least one individual affected with breast cancer (Lara_2012). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. The authors of this study report that this variant may not be the main cause of the disease as this variant generates biochemically similar changes in amino acids. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. One of the ClinVar submitters states without providing specific evidence for independent evaluation, that the variant was seen in trans with a mutation or in homozygous state in individual without severe disease for that gene (SCV000218354.3). Based on the evidence outlined above, the variant was classified as VUS-possibly benign until additional evidence of clinical or functional importance becomes available.

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

Last Updated: Jun 14, 2021

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