NM_005732.4(RAD50):c.13G>A (p.Glu5Lys) AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 30, 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:: RCV000218712.11

Allele description

NM_005732.4(RAD50):c.13G>A (p.Glu5Lys)

Gene:

RAD50:RAD50 double strand break repair protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_005732.4(RAD50):c.13G>A (p.Glu5Lys)

HGVS:

NC_000005.10:g.132557337G>A
NG_021151.2:g.5361G>A
NM_005732.4:c.13G>AMANE SELECT
NP_005723.2:p.Glu5Lys
LRG_312t1:c.13G>A
LRG_312:g.5361G>A
LRG_312p1:p.Glu5Lys
NC_000005.9:g.131893029G>A
NG_021151.1:g.5414G>A
NM_005732.3:c.13G>A

Protein change:

E5K

Links:

dbSNP: rs756334508

NCBI 1000 Genomes Browser:

rs756334508

Molecular consequence:

NM_005732.4:c.13G>A - 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

Recent activity

Clear Turn Off Turn On

Mus musculus synaptotagmin 4 (Syt4), mRNA
Mus musculus synaptotagmin 4 (Syt4), mRNA
gi|6678200|ref|NM_009308.1|

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
SCV000277558	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 30, 2023)	germline	clinical testing	Citation Link,
SCV000830747	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 13, 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

SCV000277558

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 30, 2023)

germline

clinical testing

Citation Link,

SCV000830747

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 13, 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	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 Ambry Genetics, SCV000277558.7

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

Description

The p.E5K variant (also known as c.13G>A), located in coding exon 1 of the RAD50 gene, results from a G to A substitution at nucleotide position 13. The glutamic acid at codon 5 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Invitae, SCV000830747.7

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 233223). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs756334508, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 5 of the RAD50 protein (p.Glu5Lys).

#	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: May 7, 2024

ClinVar

Relating variation to medicine