NM_024675.4(PALB2):c.140C>A (p.Ser47Tyr) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV003765422.2

Allele description [Variation Report for NM_024675.4(PALB2):c.140C>A (p.Ser47Tyr)]

NM_024675.4(PALB2):c.140C>A (p.Ser47Tyr)

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.140C>A (p.Ser47Tyr)

HGVS:

NC_000016.10:g.23637921G>T
NG_007406.1:g.8437C>A
NM_024675.4:c.140C>AMANE SELECT
NP_078951.2:p.Ser47Tyr
NP_078951.2:p.Ser47Tyr
LRG_308t1:c.140C>A
LRG_308:g.8437C>A
LRG_308p1:p.Ser47Tyr
NC_000016.9:g.23649242G>T
NM_024675.3:c.140C>A

Protein change:

S47Y

Links:

dbSNP: rs876659427

NCBI 1000 Genomes Browser:

rs876659427

Molecular consequence:

NM_024675.4:c.140C>A - missense variant - [Sequence Ontology: SO:0001583]

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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POU domain, class 2, transcription factor 2 isoform 1 [Homo sapiens]
POU domain, class 2, transcription factor 2 isoform 1 [Homo sapiens]
gi|333360875|ref|NP_001193954.1|

Protein
PREDICTED: Homo sapiens SCAN domain containing 3 (SCAND3), transcript variant X7...
PREDICTED: Homo sapiens SCAN domain containing 3 (SCAND3), transcript variant X7, mRNA
gi|2462492243|ref|XM_054329733.1|

Nucleotide
SCAN domain-containing protein 3 isoform X1 [Homo sapiens]
SCAN domain-containing protein 3 isoform X1 [Homo sapiens]
gi|2462605868|ref|XP_054210151.1|

Protein
Mus musculus lacrimal androgen-binding protein eta (Abph) mRNA, complete cds
Mus musculus lacrimal androgen-binding protein eta (Abph) mRNA, complete cds
gi|2338287|gb|AF008595.1|

Nucleotide
EXECUTIVE SUMMARY - Antiretroviral Therapy for HIV Infection in Adults and Adole...
EXECUTIVE SUMMARY - Antiretroviral Therapy for HIV Infection in Adults and Adolescents

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004695080	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2023)	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

SCV004695080

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 2023)

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004695080.1

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

Description

This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 47 of the PALB2 protein (p.Ser47Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231887). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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

ClinVar

Relating variation to medicine