NM_005732.4(RAD50):c.1424T>C (p.Leu475Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 10, 2022
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:: RCV002009832.8

Allele description [Variation Report for NM_005732.4(RAD50):c.1424T>C (p.Leu475Pro)]

NM_005732.4(RAD50):c.1424T>C (p.Leu475Pro)

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.1424T>C (p.Leu475Pro)

HGVS:

NC_000005.10:g.132589809T>C
NG_021151.2:g.37833T>C
NM_005732.4:c.1424T>CMANE SELECT
NP_005723.2:p.Leu475Pro
LRG_312t1:c.1424T>C
LRG_312:g.37833T>C
LRG_312p1:p.Leu475Pro
NC_000005.9:g.131925501T>C
NM_005732.3:c.1424T>C

Protein change:

L475P

Links:

dbSNP: rs2149841576

NCBI 1000 Genomes Browser:

rs2149841576

Molecular consequence:

NM_005732.4:c.1424T>C - 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

PREDICTED: Homo sapiens lipid droplet assembly factor 1 (LDAF1), transcript vari...
PREDICTED: Homo sapiens lipid droplet assembly factor 1 (LDAF1), transcript variant X1, mRNA
gi|2462549896|ref|XM_054313498.1|

Nucleotide
PREDICTED: Mus musculus carboxypeptidase X, M14 family member 2 (Cpxm2), transcr...
PREDICTED: Mus musculus carboxypeptidase X, M14 family member 2 (Cpxm2), transcript variant X3, mRNA
gi|755522926|ref|XM_011241864.1|

Nucleotide
PREDICTED: Mus musculus lipoma HMGIC fusion partner-like 2 (Lhfpl2), transcript ...
PREDICTED: Mus musculus lipoma HMGIC fusion partner-like 2 (Lhfpl2), transcript variant X1, mRNA
gi|1907093603|ref|XM_011244639.4|

Nucleotide
ATP synthase subunit 8 (mitochondrion) [Abies alba]
ATP synthase subunit 8 (mitochondrion) [Abies alba]
gi|2274151962|gb|UTS57089.1|

Protein
Plant sample from Carex lucennoiberica
Plant sample from Carex lucennoiberica

biosample

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
SCV002267100	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002697389	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 29, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002267100

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 10, 2022)

germline

clinical testing

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

SCV002697389

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 29, 2020)

germline

clinical testing

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

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, SCV002267100.3

#	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. This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 475 of the RAD50 protein (p.Leu475Pro).

#	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 Ambry Genetics, SCV002697389.2

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

Description

The p.L475P variant (also known as c.1424T>C), located in coding exon 9 of the RAD50 gene, results from a T to C substitution at nucleotide position 1424. The leucine at codon 475 is replaced by proline, an amino acid with similar properties. This amino acid position is not 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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine