NM_024675.4(PALB2):c.2218C>T (p.Gln740Ter) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 7, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000587693.3

Allele description [Variation Report for NM_024675.4(PALB2):c.2218C>T (p.Gln740Ter)]

NM_024675.4(PALB2):c.2218C>T (p.Gln740Ter)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.2218C>T (p.Gln740Ter)

HGVS:

NC_000016.10:g.23629936G>A
NG_007406.1:g.16422C>T
NM_024675.4:c.2218C>TMANE SELECT
NP_078951.2:p.Gln740Ter
NP_078951.2:p.Gln740Ter
LRG_308t1:c.2218C>T
LRG_308:g.16422C>T
LRG_308p1:p.Gln740Ter
NC_000016.9:g.23641257G>A
NM_024675.3:c.2218C>T

Protein change:

Q740*

Links:

dbSNP: rs1555460445

NCBI 1000 Genomes Browser:

rs1555460445

Molecular consequence:

NM_024675.4:c.2218C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Day_12_Control_3_R2
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biosample
Profile neighbors for GEO Profiles (Select 78989821) (199)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 78968174) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 78953267) (199)
GEO Profiles
SYNCRIP synaptotagmin binding cytoplasmic RNA interacting protein [Homo sapiens]
SYNCRIP synaptotagmin binding cytoplasmic RNA interacting protein [Homo sapiens]
Gene ID:10492

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000699551	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jan 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31125277, 31589614 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699551

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jan 7, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer.

Adaniel C, Salinas F, Donaire JM, Bravo ME, Peralta O, Paredes H, Aliaga N, Sola A, Neira P, Behnke C, Rodriguez T, Torres S, Lopez F, Hurtado C.

J Glob Oncol. 2019 May;5:1-14. doi: 10.1200/JGO.18.00163.

PubMed [citation]

PMID:: 31125277
PMCID:: PMC6550094

Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.

Capalbo A, Valero RA, Jimenez-Almazan J, Pardo PM, Fabiani M, Jiménez D, Simon C, Rodriguez JM.

PLoS Genet. 2019 Oct;15(10):e1008409. doi: 10.1371/journal.pgen.1008409.

PubMed [citation]

PMID:: 31589614
PMCID:: PMC6797235

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699551.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PALB2 c.2218C>T (p.Gln740X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251494 control chromosomes. c.2218C>T has been reported in the literature in one individual affected with Breast Cancer. However, this individual also carries another pathogenic variant (BRCA1 c.3817C>T, p.Gln1273Ter). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five 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 pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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