NM_007294.3(BRCA1):c.301+10G>A AND not specified

Clinical significance:Likely benign (Last evaluated: Aug 27, 2021)

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:
RCV000609750.2

Allele description [Variation Report for NM_007294.3(BRCA1):c.301+10G>A]

NM_007294.3(BRCA1):c.301+10G>A

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.301+10G>A
Other names:
IVS6+10G>A
HGVS:
  • NC_000017.11:g.43104858C>T
  • NG_005905.2:g.113126G>A
  • NM_007294.3:c.301+10G>A
  • NM_007297.4:c.160+10G>A
  • NM_007298.3:c.301+10G>A
  • NM_007299.4:c.301+10G>A
  • NM_007300.4:c.301+10G>A
  • LRG_292t1:c.301+10G>A
  • LRG_292:g.113126G>A
  • NC_000017.10:g.41256875C>T
  • U14680.1:n.420+10G>A
Links:
Breast Cancer Information Core (BIC) (BRCA1): 420+10&base_change=G to A; dbSNP: rs80358001
NCBI 1000 Genomes Browser:
rs80358001
Molecular consequence:
  • NM_007294.3:c.301+10G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.160+10G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.301+10G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.301+10G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.301+10G>A - intron variant - [Sequence Ontology: SO:0001627]
Functional consequence:
functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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
SCV000732717GeneDxcriteria provided, single submitter
Likely benign
(Jun 22, 2017)
germlineclinical testing

Citation Link,

SCV001821405Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Aug 27, 2021)
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

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]
PMID:
30209399
PMCID:
PMC6181777

Details of each submission

From GeneDx, SCV000732717.1

#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, SCV001821405.1

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

Description

Variant summary: BRCA1 c.301+10G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251148 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.301+10G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. At least one functional study reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. This working group has recommended strong functional evidence (ACMG BS3) as sufficient weightage for categorization as likely benign (Tavtigian_2018). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Sep 7, 2021

Support Center