NC_000016.10:g.(?_23603449)_(23614101_?)del AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 2018
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:: RCV000817957.2

Allele description [Variation Report for NC_000016.10:g.(?_23603449)_(23614101_?)del]

NC_000016.10:g.(?_23603449)_(23614101_?)del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NC_000016.10:g.(?_23603449)_(23614101_?)del

HGVS:

NC_000016.10:g.(?_23603449)_(23614101_?)del
NC_000016.9:g.(?_23614770)_(23625422_?)del

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000958544	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2018)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25099575, 17200671, 16793542, 19423707, 17200668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000958544

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2018)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Breast-cancer risk in families with mutations in PALB2.

Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F, Tomiak E, Neuhausen SL, Teo ZL, Khan S, Aittomäki K, Moilanen JS, Turnbull C, Seal S, Mannermaa A, Kallioniemi A, Lindeman GJ, Buys SS, et al.

N Engl J Med. 2014 Aug 7;371(6):497-506. doi: 10.1056/NEJMoa1400382.

PubMed [citation]

PMID:: 25099575
PMCID:: PMC4157599

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.

Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N.

Nat Genet. 2007 Feb;39(2):162-4. Epub 2006 Dec 31.

PubMed [citation]

PMID:: 17200671

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000958544.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is a gross deletion of the genomic region encompassing exons 11-13 of the PALB2 gene. The 5' boundary is likely confined to intron 12. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated PALB2 protein. While this particular variant has not been reported in the literature, loss-of-function variants in PALB2 are known to be pathogenic (PMID: 25099575, 17200668). This deletion eliminates a portion of the WD40 functional domain, which is encoded by exons 7 to 13 of the PALB2 mRNA. The entire WD40 domain is required for normal PALB2 protein function (PMID: 19423707, 16793542, 17200671), and loss-of-function mutations that disrupt this domain have been classified as pathogenic (Invitae). This deletion is likely to truncate the PALB2 protein and abolish its DNA repair function. For these reasons, this variant has been classified as 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: Dec 11, 2022

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