NM_024675.4(PALB2):c.3299_3306dup (p.Val1103fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2017
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:: RCV000657412.2

Allele description [Variation Report for NM_024675.4(PALB2):c.3299_3306dup (p.Val1103fs)]

NM_024675.4(PALB2):c.3299_3306dup (p.Val1103fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.3299_3306dup (p.Val1103fs)

HGVS:

NC_000016.10:g.23607908_23607915dup
NG_007406.1:g.38443_38450dup
NM_024675.4:c.3299_3306dupMANE SELECT
NP_078951.2:p.Val1103fs
NP_078951.2:p.Val1103fs
LRG_308t1:c.3299_3306dup
LRG_308:g.38443_38450dup
LRG_308p1:p.Val1103fs
NC_000016.9:g.23619228_23619229insGCTGAGAG
NC_000016.9:g.23619229_23619236dup
NM_024675.3:c.3299_3306dup
NM_024675.3:c.3299_3306dupCTCTCAGC

Protein change:

V1103fs

Links:

dbSNP: rs1555458187

NCBI 1000 Genomes Browser:

rs1555458187

Molecular consequence:

NM_024675.4:c.3299_3306dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779147	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Nov 15, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779147

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Nov 15, 2017)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000779147.2

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

Description

This duplication of eight nucleotides in PALB2 is denoted c.3299_3306dupCTCTCAGC at the cDNA level and p.Val1103LeufsX6 (V1103LfsX6) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is ACGA[dupCTCTCAGC]GTGG. The duplication causes a frameshift which changes a Valine to a Leucine at codon 1103, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation. The last 84 correct amino acids are replaced by 5 incorrect ones, disrupting the regions required for interaction with POLH and POLH DNA synthesis stimulation, Rad51, and BRCA2, as well as the last 3 (WD5-7) WD repeats (Oliver 2009, Buisson 2010, Buisson 2014, UniProt). We consider this variant to be pathogenic.

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

Last Updated: Sep 29, 2024

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