NM_024675.3(PALB2):c.2515-1G>C AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: May 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000580827.3

Allele description [Variation Report for NM_024675.3(PALB2):c.2515-1G>C]

NM_024675.3(PALB2):c.2515-1G>C

Gene:
PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p12.2
Genomic location:
Preferred name:
NM_024675.3(PALB2):c.2515-1G>C
HGVS:
  • NC_000016.10:g.23629276C>G
  • NG_007406.1:g.17082G>C
  • NM_024675.3:c.2515-1G>C
  • LRG_308t1:c.2515-1G>C
  • LRG_308:g.17082G>C
  • NC_000016.9:g.23640597C>G
Links:
dbSNP: rs587776417
NCBI 1000 Genomes Browser:
rs587776417
Molecular consequence:
  • NM_024675.3:c.2515-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

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
SCV000685956Color Health, Inccriteria provided, single submitter
Likely pathogenic
(Aug 11, 2018)
germlineclinical testing

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

SCV001176611Ambry Geneticscriteria provided, single submitter
Uncertain significance
(May 7, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

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, SCV000685956.2

#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, SCV001176611.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.2515-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 6 of the PALB2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are are typically deleterious in nature, however, this alteration occurs at a splice site in which <span style="font-family:open sans,helvetica neue,helvetica,arial,sans-serif">naturally occurring alternative splicing events have been described. The exact functional impact of this alteration is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: May 10, 2021

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