NM_024675.4(PALB2):c.212-1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 16, 2020
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:: RCV001180262.4

Allele description [Variation Report for NM_024675.4(PALB2):c.212-1G>A]

NM_024675.4(PALB2):c.212-1G>A

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.212-1G>A

HGVS:

NC_000016.10:g.23636335C>T
NG_007406.1:g.10023G>A
NM_001407296.1:c.152-1G>A
NM_001407297.1:c.212-1G>A
NM_001407298.1:c.212-1G>A
NM_001407299.1:c.212-1G>A
NM_001407300.1:c.212-1G>A
NM_001407301.1:c.212-1G>A
NM_001407302.1:c.212-1G>A
NM_001407304.1:c.-674-1G>A
NM_001407305.1:c.-674-1G>A
NM_001407306.1:c.-674-1G>A
NM_001407307.1:c.-674-1G>A
NM_001407308.1:c.-674-1G>A
NM_001407309.1:c.-674-1G>A
NM_001407310.1:c.-674-1G>A
NM_001407311.1:c.-674-1G>A
NM_001407312.1:c.-105+4775G>A
NM_001407313.1:c.-105+4775G>A
NM_001407314.1:c.48+4775G>A
NM_024675.4:c.212-1G>AMANE SELECT
LRG_308t1:c.212-1G>A
LRG_308:g.10023G>A
NC_000016.9:g.23647656C>T
NC_000016.9:g.23647656C>T
NM_024675.3:c.212-1G>A

Links:

dbSNP: rs1597099910

NCBI 1000 Genomes Browser:

rs1597099910

Molecular consequence:

NM_001407312.1:c.-105+4775G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407313.1:c.-105+4775G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407314.1:c.48+4775G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.152-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407297.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407298.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407299.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407300.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407301.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407302.1:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407304.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407305.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407306.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407307.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407308.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407309.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407310.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407311.1:c.-674-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_024675.4:c.212-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Homo sapiens coiled-coil domain containing 9B (CCDC9B), mRNA
Homo sapiens coiled-coil domain containing 9B (CCDC9B), mRNA
gi|1967468169|ref|NM_207380.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001345142	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001345142

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 16, 2020)

germline

clinical testing

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

Help

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

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 Diagnostics, LLC DBA Color Health, SCV001345142.2

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

Description

This variant causes a G to A nucleotide substitution at the -1 position of intron 3 of the PALB2 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. A minigene assay has shown that the variant causes skipping of exon 4 and 5 (PMID: 30890586), which is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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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