NM_024675.4(PALB2):c.3114-554_3166del AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 8, 2023
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:: RCV003360866.2

Allele description [Variation Report for NM_024675.4(PALB2):c.3114-554_3166del]

NM_024675.4(PALB2):c.3114-554_3166del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.3114-554_3166del

HGVS:

NC_000016.10:g.23614039_23614645del
NG_007406.1:g.31713_32319del
NM_001407296.1:c.3054-554_3106del
NM_001407297.1:c.3042-554_3094del
NM_001407298.1:c.2952-554_3004del
NM_001407299.1:c.3113+6717_3113+7323del
NM_001407300.1:c.2835-554_2887del
NM_001407301.1:c.3114-554_3166del
NM_001407302.1:c.2952-554_3004del
NM_001407304.1:c.2229-554_2281del
NM_001407305.1:c.2229-554_2281del
NM_001407306.1:c.2229-554_2281del
NM_001407307.1:c.2067-554_2119del
NM_001407308.1:c.2228+6717_2228+7323del
NM_001407309.1:c.2228+6717_2228+7323del
NM_001407310.1:c.2229-554_2281del
NM_001407311.1:c.2229-554_2281del
NM_001407312.1:c.1326-554_1378del
NM_001407313.1:c.1326-554_1378del
NM_001407314.1:c.648-554_700del
NM_024675.4:c.3114-554_3166delMANE SELECT
LRG_308t1:c.3114-554_3166del607
LRG_308:g.31713_32319del
NC_000016.9:g.23625360_23625966del
NM_024675.3:c.3114-554_3166del607

Molecular consequence:

NM_001407299.1:c.3113+6717_3113+7323del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407308.1:c.2228+6717_2228+7323del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407309.1:c.2228+6717_2228+7323del - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.3054-554_3106del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407297.1:c.3042-554_3094del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407298.1:c.2952-554_3004del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407300.1:c.2835-554_2887del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407301.1:c.3114-554_3166del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407302.1:c.2952-554_3004del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407304.1:c.2229-554_2281del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407305.1:c.2229-554_2281del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407306.1:c.2229-554_2281del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407307.1:c.2067-554_2119del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407310.1:c.2229-554_2281del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407311.1:c.2229-554_2281del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407312.1:c.1326-554_1378del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407313.1:c.1326-554_1378del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407314.1:c.648-554_700del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_024675.4:c.3114-554_3166del - 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

Recent activity

Clear Turn Off Turn On

RYBP [Capra hircus]
RYBP [Capra hircus]
Gene ID:102189529

Gene
Atxn2 [Peromyscus maniculatus bairdii]
Atxn2 [Peromyscus maniculatus bairdii]
Gene ID:102921483

Gene
Syf2 [Jaculus jaculus]
Syf2 [Jaculus jaculus]
Gene ID:101597493

Gene
SPATS2L [Capra hircus]
SPATS2L [Capra hircus]
Gene ID:102186063

Gene
YCL030c, len:799 [Saccharomyces cerevisiae]
YCL030c, len:799 [Saccharomyces cerevisiae]
gi|5334|emb|CAA42355.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004057664	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Sep 8, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004057664

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Sep 8, 2023)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV004057664.2

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

Description

The complex rearrangement is an Alu-mediated deletion involving an Alu insertion (c.3179_3180insAlu) and a deletion of 607 nucleotides between positions c.3114-554 and c.3166 and involves the canonical splice acceptor site before coding exon 11 of the PALB2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). 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

ClinVar

Relating variation to medicine