NM_000059.3(BRCA2):c.1219C>T (p.Gln407Ter) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2020)

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:
RCV000583844.3

Allele description [Variation Report for NM_000059.3(BRCA2):c.1219C>T (p.Gln407Ter)]

NM_000059.3(BRCA2):c.1219C>T (p.Gln407Ter)

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.1219C>T (p.Gln407Ter)
HGVS:
  • NC_000013.11:g.32332697C>T
  • NG_012772.3:g.22218C>T
  • NM_000059.3:c.1219C>T
  • NP_000050.2:p.Gln407Ter
  • LRG_293t1:c.1219C>T
  • LRG_293:g.22218C>T
  • LRG_293p1:p.Gln407Ter
  • NC_000013.10:g.32906834C>T
Protein change:
Q407*
Links:
dbSNP: rs781079248
NCBI 1000 Genomes Browser:
rs781079248
Molecular consequence:
  • NM_000059.3:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000688700Color Health, Inccriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

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

SCV001170594Ambry Geneticscriteria provided, single submitter
Pathogenic
(Aug 6, 2018)
germlineclinical testing

Citation Link

Description

This variant changes 1 nucleotide in exon 10 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

SCV000688700

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Health, Inc, SCV000688700.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV001170594.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.Q407* pathogenic mutation (also known as c.1219C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 1219. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jun 14, 2021

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