NM_024675.4(PALB2):c.437GAA[1] (p.Arg147del) AND Familial cancer of breast

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000410910.11

Allele description [Variation Report for NM_024675.4(PALB2):c.437GAA[1] (p.Arg147del)]

NM_024675.4(PALB2):c.437GAA[1] (p.Arg147del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.437GAA[1] (p.Arg147del)

HGVS:

NC_000016.10:g.23636105TCT[1]
NG_007406.1:g.10249GAA[1]
NM_024675.4:c.437GAA[1]MANE SELECT
NP_078951.2:p.Arg147del
LRG_308t1:c.440_442del
LRG_308:g.10249GAA[1]
NC_000016.9:g.23647425_23647427del
NC_000016.9:g.23647426TCT[1]
NM_024675.3:c.440_442del
NM_024675.3:c.440_442delGAA
NM_024675.4:c.440_442delMANE SELECT

Protein change:

R147del

Links:

dbSNP: rs760629975

NCBI 1000 Genomes Browser:

rs760629975

Molecular consequence:

NM_024675.4:c.437GAA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

Recent activity

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Puccinia coronata f. sp. avenae isolate 12NC29 000553F, whole genome shotgun seq...
Puccinia coronata f. sp. avenae isolate 12NC29 000553F, whole genome shotgun sequence
gi|1321542143|gb|PGCJ01000496.1||gn :PGCJ01|000553F

Nucleotide
Puccinia coronata f. sp. avenae isolate 12SD80 000428F, whole genome shotgun seq...
Puccinia coronata f. sp. avenae isolate 12SD80 000428F, whole genome shotgun sequence
gi|1321542790|gb|PGCI01000390.1||gn :PGCI01|000428F

Nucleotide
Puccinia coronata f. sp. avenae isolate 12SD80 000275F_001, whole genome shotgun...
Puccinia coronata f. sp. avenae isolate 12SD80 000275F_001, whole genome shotgun sequence
gi|1321523112|gb|PGCI01000989.1||gn :PGCI01|000275F_001

Nucleotide
Puccinia coronata f. sp. avenae isolate 12SD80 000060F_004, whole genome shotgun...
Puccinia coronata f. sp. avenae isolate 12SD80 000060F_004, whole genome shotgun sequence
gi|1321523297|gb|PGCI01000982.1||gn :PGCI01|000060F_004

Nucleotide
Puccinia coronata f. sp. avenae isolate 12SD80 000087F_003, whole genome shotgun...
Puccinia coronata f. sp. avenae isolate 12SD80 000087F_003, whole genome shotgun sequence
gi|1321522249|gb|PGCI01001029.1||gn :PGCI01|000087F_003

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000488079	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Dec 22, 2015)	unknown	clinical testing	Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000550652	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004019213	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Mar 30, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000488079

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Dec 22, 2015)

unknown

clinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV000550652

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 11, 2022)

germline

clinical testing

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

SCV004019213

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Uncertain significance
(Mar 30, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Counsyl, SCV000488079.2

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550652.6

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 371807). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is present in population databases (rs760629975, gnomAD 0.0009%). This variant, c.440_442del, results in the deletion of 1 amino acid(s) of the PALB2 protein (p.Arg147del), but otherwise preserves the integrity of the reading frame.

#	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

From Myriad Genetics, Inc., SCV004019213.1

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

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

Last Updated: Sep 29, 2024

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