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NM_024675.4(PALB2):c.1751ATG[4] (p.Asp586dup) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jul 8, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000564754.5

Allele description [Variation Report for NM_024675.4(PALB2):c.1751ATG[4] (p.Asp586dup)]

NM_024675.4(PALB2):c.1751ATG[4] (p.Asp586dup)

Gene:
PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
16p12.2
Genomic location:
Preferred name:
NM_024675.4(PALB2):c.1751ATG[4] (p.Asp586dup)
HGVS:
  • NC_000016.10:g.23630396ATC[4]
  • NG_007406.1:g.15955ATG[4]
  • NM_024675.4:c.1751ATG[4]MANE SELECT
  • NP_078951.2:p.Asp586dup
  • LRG_308t1:c.1757_1759dup
  • LRG_308:g.15955ATG[4]
  • NC_000016.9:g.23641715_23641716insCAT
  • NC_000016.9:g.23641717ATC[4]
  • NM_024675.3:c.1757_1759dup
  • NM_024675.3:c.1757_1759dupATG
  • NM_024675.4:c.1757_1759dupMANE SELECT
Links:
dbSNP: rs1555460665
NCBI 1000 Genomes Browser:
rs1555460665
Molecular consequence:
  • NM_024675.4:c.1751ATG[4] - inframe_insertion - [Sequence Ontology: SO:0001821]
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; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000665164Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Uncertain significance
(Jul 8, 2022) 		germlineclinical testing

Citation Link,

SCV004357901Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 31, 2022) 		germlineclinical testing

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

Help

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 Ambry Genetics, SCV000665164.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.1757_1759dupATG variant (also known as p.D586dup), located in coding exon 5 of the PALB2 gene, results from an in-frame duplication of ATG at nucleotide positions 1757 to 1759. This results in the duplication of an extra residue between codons 586 and 587. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). 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

From Color Diagnostics, LLC DBA Color Health, SCV004357901.1

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

Description

This variant causes the duplication of 3 basepairs resulting in the in-frame duplication of Aspartic acid 586 in the PALB2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ovarian cancer (ClinVar variation ID: 403713). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Feb 20, 2024