NM_000136.3(FANCC):c.346-1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 22, 2022
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:: RCV002334038.2

Allele description [Variation Report for NM_000136.3(FANCC):c.346-1G>A]

NM_000136.3(FANCC):c.346-1G>A

Gene:

FANCC:FA complementation group C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.346-1G>A

HGVS:

NC_000009.12:g.95172148C>T
NG_011707.1:g.150562G>A
NM_000136.3:c.346-1G>AMANE SELECT
NM_001243743.2:c.346-1G>A
NM_001243744.2:c.346-1G>A
LRG_497t1:c.346-1G>A
LRG_497:g.150562G>A
NC_000009.11:g.97934430C>T
NM_000136.2:c.346-1G>A
NM_001243743.1:c.346-1G>A

Links:

dbSNP: rs1484503633

NCBI 1000 Genomes Browser:

rs1484503633

Molecular consequence:

NM_000136.3:c.346-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001243743.2:c.346-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001243744.2:c.346-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

Clear Turn Off Turn On

Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript var...
Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript variant 10, mRNA
gi|1677501263|ref|NM_001352350.2|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002618654	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26556299, 31300551 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002618654

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 22, 2022)

germline

clinical testing

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

Citation Link

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

Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

Schrader KA, Cheng DT, Joseph V, Prasad M, Walsh M, Zehir A, Ni A, Thomas T, Benayed R, Ashraf A, Lincoln A, Arcila M, Stadler Z, Solit D, Hyman DM, Zhang L, Klimstra D, Ladanyi M, Offit K, Berger M, Robson M.

JAMA Oncol. 2016 Jan;2(1):104-11. doi: 10.1001/jamaoncol.2015.5208. Erratum in: JAMA Oncol. 2016 Feb;2(2):279. doi: 10.1001/jamaoncol.2015.6541. Hyman, David [corrected to Hyman, David M].

PubMed [citation]

PMID:: 26556299
PMCID:: PMC5477989

One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene.

Fostira F, Kostantopoulou I, Apostolou P, Papamentzelopoulou MS, Papadimitriou C, Faliakou E, Christodoulou C, Boukovinas I, Razis E, Tryfonopoulos D, Barbounis V, Vagena A, Vlachos IS, Kalfakakou D, Fountzilas G, Yannoukakos D.

J Med Genet. 2020 Jan;57(1):53-61. doi: 10.1136/jmedgenet-2019-106189. Epub 2019 Jul 12.

PubMed [citation]

PMID:: 31300551
PMCID:: PMC6929701

Details of each submission

From Ambry Genetics, SCV002618654.2

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

Description

The c.346-1G>A intronic variant results from a G to A substitution one nucleotide before coding exon 4 of the FANCC gene. This alteration has been reported in the germline of an individual with salivary carcinoma from a cohort of patients with advanced cancer diagnoses who underwent tumor-normal sequencing (Schrader KA et al. JAMA Oncol, 2016 Jan;2:104-11). This alteration has also been reported in an individual diagnosed with early-onset breast cancer (Fostira F et al. J. Med. Genet., 2020 01;57:53-61). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that the strength of the native acceptor splice site is maintained, but shifted upstream one nucleotide resulting in a translational frameshift with a predicted alternate stop codon; however, direct evidence is unavailable. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

#	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