NM_024675.4(PALB2):c.1935G>A (p.Glu645=) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (4 submissions)
Last evaluated:: Jan 23, 2022
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:: RCV000167184.9

Allele description [Variation Report for NM_024675.4(PALB2):c.1935G>A (p.Glu645=)]

NM_024675.4(PALB2):c.1935G>A (p.Glu645=)

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.1935G>A (p.Glu645=)

HGVS:

NC_000016.10:g.23630219C>T
NG_007406.1:g.16139G>A
NM_024675.4:c.1935G>AMANE SELECT
NP_078951.2:p.Glu645=
NP_078951.2:p.Glu645=
LRG_308t1:c.1935G>A
LRG_308:g.16139G>A
LRG_308p1:p.Glu645=
NC_000016.9:g.23641540C>T
NM_024675.3:c.1935G>A
p.E645E

Links:

dbSNP: rs141707455

NCBI 1000 Genomes Browser:

rs141707455

Molecular consequence:

NM_024675.4:c.1935G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; 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
SCV000218020	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Aug 5, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21618343, 23448497 Citation Link,
SCV000690818	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 26, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000886696	True Health Diagnostics	no assertion criteria provided	Likely benign (Sep 6, 2018)	germline	clinical testing
SCV002530660	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Jan 23, 2022)	germline	curation	Citation Link

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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, curation

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

Prevalence of PALB2 mutations in Australasian multiple-case breast cancer families.

Teo ZL, Park DJ, Provenzano E, Chatfield CA, Odefrey FA, Nguyen-Dumont T; kConFab, Dowty JG, Hopper JL, Winship I, Goldgar DE, Southey MC.

Breast Cancer Res. 2013 Feb 28;15(1):R17. doi: 10.1186/bcr3392.

PubMed [citation]

PMID:: 23448497
PMCID:: PMC3672826

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000218020.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000690818.2

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

#	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 True Health Diagnostics, SCV000886696.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002530660.1

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

#	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: Jul 13, 2025

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