NM_024675.4(PALB2):c.2228A>G (p.Tyr743Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Aug 27, 2018
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:: RCV000164010.14

Allele description [Variation Report for NM_024675.4(PALB2):c.2228A>G (p.Tyr743Cys)]

NM_024675.4(PALB2):c.2228A>G (p.Tyr743Cys)

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.2228A>G (p.Tyr743Cys)

HGVS:

NC_000016.10:g.23629926T>C
NG_007406.1:g.16432A>G
NM_024675.4:c.2228A>GMANE SELECT
NP_078951.2:p.Tyr743Cys
NP_078951.2:p.Tyr743Cys
LRG_308t1:c.2228A>G
LRG_308:g.16432A>G
LRG_308p1:p.Tyr743Cys
NC_000016.9:g.23641247T>C
NM_024675.3:c.2228A>G
p.Y743C

Protein change:

Y743C

Links:

dbSNP: rs141749524

NCBI 1000 Genomes Browser:

rs141749524

Molecular consequence:

NM_024675.4:c.2228A>G - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000214615	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Aug 27, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26283626, 26411315 Citation Link,
SCV000396098	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Likely benign (Jun 14, 2016)	germline	clinical testing	ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV000902864	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 10, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000214615

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Aug 27, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000396098

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification 20161018)

Likely benign
(Jun 14, 2016)

germline

clinical testing

ICSL_Variant_Classification_20161018.pdf,

Citation Link,

SCV000902864

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Nov 10, 2015)

germline

clinical testing

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

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

Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls.

Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, Trainer AH, Devereux L, Doyle MA, Li J, Lupat R, Delatycki MB; LifePool Investigators., Mitchell G, James PA, Scott RJ, Campbell IG.

Breast Cancer Res. 2015 Aug 19;17:111. doi: 10.1186/s13058-015-0627-7.

PubMed [citation]

PMID:: 26283626
PMCID:: PMC4539664

Analysis of PALB2 mutations in 155 Japanese patients with breast and/or ovarian cancer.

Nakagomi H, Sakamoto I, Hirotsu Y, Amemiya K, Mochiduki H, Omata M.

Int J Clin Oncol. 2016 Apr;21(2):270-275. doi: 10.1007/s10147-015-0906-4. Epub 2015 Sep 28.

PubMed [citation]

PMID:: 26411315

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000214615.7

#	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 Illumina Laboratory Services, Illumina, SCV000396098.2

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

From Color Diagnostics, LLC DBA Color Health, SCV000902864.1

#	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

Last Updated: Sep 29, 2024

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