NM_024675.4(PALB2):c.3508C>T (p.His1170Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Sep 9, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000129794.20

Allele description [Variation Report for NM_024675.4(PALB2):c.3508C>T (p.His1170Tyr)]

NM_024675.4(PALB2):c.3508C>T (p.His1170Tyr)

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.3508C>T (p.His1170Tyr)

Other names:

p.H1170Y:CAT>TAT

HGVS:

NC_000016.10:g.23603512G>A
NG_007406.1:g.42846C>T
NM_024675.4:c.3508C>TMANE SELECT
NP_078951.2:p.His1170Tyr
NP_078951.2:p.His1170Tyr
LRG_308t1:c.3508C>T
LRG_308:g.42846C>T
LRG_308p1:p.His1170Tyr
NC_000016.9:g.23614833G>A
NM_024675.3:c.3508C>T
Q86YC2:p.His1170Tyr
p.H1170Y

Protein change:

H1170Y

Links:

UniProtKB: Q86YC2#VAR_066384; dbSNP: rs200283306

NCBI 1000 Genomes Browser:

rs200283306

Molecular consequence:

NM_024675.4:c.3508C>T - 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
SCV000184603	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 9, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21618343, 24448499, 26315354, 26689913, 28591191, 29052111 Citation Link,
SCV000822118	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000910786	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Nov 25, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002531187	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Dec 17, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 29052111, 33471991 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
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

Integrated analysis of germline and somatic variants in ovarian cancer.

Kanchi KL, Johnson KJ, Lu C, McLellan MD, Leiserson MD, Wendl MC, Zhang Q, Koboldt DC, Xie M, Kandoth C, McMichael JF, Wyczalkowski MA, Larson DE, Schmidt HK, Miller CA, Fulton RS, Spellman PT, Mardis ER, Druley TE, Graubert TA, Goodfellow PJ, Raphael BJ, et al.

Nat Commun. 2014;5:3156. doi: 10.1038/ncomms4156.

PubMed [citation]

PMID:: 24448499
PMCID:: PMC4025965

See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000184603.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

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 GeneKor MSA, SCV000822118.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000910786.1

#	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

From Sema4, Sema4, SCV002531187.1

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

#	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: Oct 20, 2024

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