NM_024675.4(PALB2):c.48+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 16, 2015
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:: RCV000213648.4

Allele description [Variation Report for NM_024675.4(PALB2):c.48+1G>C]

NM_024675.4(PALB2):c.48+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_024675.4(PALB2):c.48+1G>C

HGVS:

NC_000016.10:g.23641109C>G
NG_007406.1:g.5249G>C
NM_001407296.1:c.48+1G>C
NM_001407297.1:c.48+1G>C
NM_001407298.1:c.48+1G>C
NM_001407299.1:c.48+1G>C
NM_001407300.1:c.48+1G>C
NM_001407301.1:c.48+1G>C
NM_001407302.1:c.48+1G>C
NM_001407304.1:c.-1695G>C
NM_001407305.1:c.-972+1G>C
NM_001407306.1:c.-838+18G>C
NM_001407307.1:c.-972+1G>C
NM_001407308.1:c.-838+18G>C
NM_001407309.1:c.-972+1G>C
NM_001407310.1:c.-1695G>C
NM_001407311.1:c.-972+1G>C
NM_001407312.1:c.-105+1G>C
NM_001407313.1:c.-105+1G>C
NM_001407314.1:c.48+1G>C
NM_024675.4:c.48+1G>CMANE SELECT
LRG_308t1:c.48+1G>C
LRG_308:g.5249G>C
NC_000016.9:g.23652430C>G
NM_024675.3:c.48+1G>C

Links:

dbSNP: rs515726118

NCBI 1000 Genomes Browser:

rs515726118

Molecular consequence:

NM_001407304.1:c.-1695G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407310.1:c.-1695G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407306.1:c.-838+18G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407308.1:c.-838+18G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407297.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407298.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407299.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407300.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407301.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407302.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407305.1:c.-972+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407307.1:c.-972+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407309.1:c.-972+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407311.1:c.-972+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407312.1:c.-105+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407313.1:c.-105+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407314.1:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_024675.4:c.48+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000274677	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 16, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000274677

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 16, 2015)

germline

clinical testing

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

Citation Link

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

Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer.

Hellebrand H, Sutter C, Honisch E, Gross E, Wappenschmidt B, Schem C, Deissler H, Ditsch N, Gress V, Kiechle M, Bartram CR, Schmutzler RK, Niederacher D, Arnold N, Meindl A.

Hum Mutat. 2011 Jun;32(6):E2176-88. doi: 10.1002/humu.21478. Epub 2011 Feb 24.

PubMed [citation]

PMID:: 21618343

Details of each submission

From Ambry Genetics, SCV000274677.7

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

Description

The c.48+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 1 of the PALB2 gene. This variant was first reported in an individual with breast cancer and family history of breast cancer (Hellebrand H, et al. Hum. Mutat. 2011 Jun; 32(6):E2176-88). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration 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: May 1, 2024

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