NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Aug 2, 2023
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:: RCV000480509.18

Allele description [Variation Report for NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter)]

NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter)

HGVS:

NC_000013.11:g.32338577C>T
NG_012772.3:g.28098C>T
NM_000059.4:c.4222C>TMANE SELECT
NP_000050.2:p.Gln1408Ter
NP_000050.3:p.Gln1408Ter
LRG_293t1:c.4222C>T
LRG_293:g.28098C>T
LRG_293p1:p.Gln1408Ter
NC_000013.10:g.32912714C>T
NM_000059.3:c.4222C>T
U43746.1:n.4450C>T
p.Gln1408*

Nucleotide change:

4450C>T

Protein change:

Q1408*

Links:

dbSNP: rs80358663

NCBI 1000 Genomes Browser:

rs80358663

Molecular consequence:

NM_000059.4:c.4222C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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ATP synthase F0 subunit 8 (mitochondrion) [Propithecus edwardsi]
ATP synthase F0 subunit 8 (mitochondrion) [Propithecus edwardsi]
gi|2267398481|gb|UTE81815.1|

Protein
CD109 [Mauremys reevesii]
CD109 [Mauremys reevesii]
Gene ID:120399972

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567660	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 2, 2023)	germline	clinical testing	Citation Link,
SCV000600581	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 19, 2022)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 28888541, 20104584, 29446198, 29907814, 30103829, 22009639, 19818148, 26467025
SCV003813828	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 21, 2022)	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

SCV000567660

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 2, 2023)

germline

clinical testing

Citation Link,

SCV000600581

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Aug 19, 2022)

unknown

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV003813828

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 21, 2022)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	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

Citations

PubMed

Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls.

Lilyquist J, LaDuca H, Polley E, Davis BT, Shimelis H, Hu C, Hart SN, Dolinsky JS, Couch FJ, Goldgar DE.

Gynecol Oncol. 2017 Nov;147(2):375-380. doi: 10.1016/j.ygyno.2017.08.030. Epub 2017 Sep 7.

PubMed [citation]

PMID:: 28888541
PMCID:: PMC5801741

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000567660.6

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with breast and/or ovarian cancer (Miolo et al., 2009; Bayraktar et al., 2012; Cardoso et al., 2018; Liang et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4450C>T; This variant is associated with the following publications: (PMID: 30787465, 19818148, 22009639, 29681614, 29446198, 30103829, 29907814, 28888541, 32377563, 36556183, 34308104)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600581.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with personal and/or family history of breast and/or ovarian cancer (PMID: 30103829 (2018), 29907814 (2018), 28888541 (2017), 22009639 (2012), 20104584 (2010), 19818148 (2009)). Based on the available information, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003813828.2

#	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

Last Updated: Nov 10, 2024

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