NM_002485.5(NBN):c.2149A>T (p.Thr717Ser) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 11, 2021
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:: RCV000780522.6

Allele description [Variation Report for NM_002485.5(NBN):c.2149A>T (p.Thr717Ser)]

NM_002485.5(NBN):c.2149A>T (p.Thr717Ser)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.2149A>T (p.Thr717Ser)

Other names:

p.T717S:ACA>TCA

HGVS:

NC_000008.11:g.89943288T>A
NG_008860.1:g.46384A>T
NM_001024688.3:c.1903A>T
NM_002485.5:c.2149A>TMANE SELECT
NP_001019859.1:p.Thr635Ser
NP_002476.2:p.Thr717Ser
NP_002476.2:p.Thr717Ser
LRG_158t1:c.2149A>T
LRG_158:g.46384A>T
LRG_158p1:p.Thr717Ser
NC_000008.10:g.90955516T>A
NM_002485.4:c.2149A>T
p.T717S

Protein change:

T635S

Links:

dbSNP: rs587780093

NCBI 1000 Genomes Browser:

rs587780093

Molecular consequence:

NM_001024688.3:c.1903A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.2149A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

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
SCV000917850	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 12, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002065379	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 11, 2021)	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

SCV000917850

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 12, 2017)

germline

clinical testing

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

Citation Link,

SCV002065379

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 11, 2021)

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	no	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

Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes.

Al-Hebshi NN, Li S, Nasher AT, El-Setouhy M, Alsanosi R, Blancato J, Loffredo C.

Int J Cancer. 2016 Jul 15;139(2):363-72. doi: 10.1002/ijc.30068. Epub 2016 Mar 18.

PubMed [citation]

PMID:: 26934577
PMCID:: PMC5821466

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917850.1

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

Description

Variant summary: The NBN c.2149A>T (p.Thr717Ser) variant located in the DNA repair Nbs1, C-terminal domain (via InterPro) involves the alteration of a non-conserved nucleotide and 5/5 in silico tools predict a benign outcome for this variant. However, these predictions have yet to be functionally assessed. This variant is absent in 121388 control chromosomes and has not, to our knowledge been reported in affected indivduals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

#	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 Genetic Services Laboratory, University of Chicago, SCV002065379.1

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

Description

DNA sequence analysis of the NBN gene demonstrated a sequence change, c.2149A>T, in exon 14 that results in an amino acid change, p.Thr717Ser. This sequence change has not been described in the gnomAD database. The p.Thr717Ser change affects a poorly conserved amino acid residue located in a domain of the NBN protein that is known to be functional. The p.Thr717Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has been reported as a variant of uncertain significance in an individual who underwent germline genetic testing based on a personal and/or family history of cancer (PMID: 31159747). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr717Ser change remains unknown at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine