NM_005732.4(RAD50):c.1097C>G (p.Ala366Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 12, 2020
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:: RCV001299430.7

Allele description [Variation Report for NM_005732.4(RAD50):c.1097C>G (p.Ala366Gly)]

NM_005732.4(RAD50):c.1097C>G (p.Ala366Gly)

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.1097C>G (p.Ala366Gly)

HGVS:

NC_000005.10:g.132588732C>G
NG_021151.2:g.36756C>G
NM_005732.4:c.1097C>GMANE SELECT
NP_005723.2:p.Ala366Gly
LRG_312t1:c.1097C>G
LRG_312:g.36756C>G
LRG_312p1:p.Ala366Gly
NC_000005.9:g.131924424C>G
NG_021151.1:g.36809C>G

Protein change:

A366G

Links:

dbSNP: rs1580992732

NCBI 1000 Genomes Browser:

rs1580992732

Molecular consequence:

NM_005732.4:c.1097C>G - 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

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zinc finger protein 567 isoform 1 [Homo sapiens]
zinc finger protein 567 isoform 1 [Homo sapiens]
gi|1915469478|ref|NP_001374691.1|

Protein
Guanosine Diphosphate Fucose
Guanosine Diphosphate Fucose
A nucleoside diphosphate sugar formed from GDPmannose, which provides fucose for lipopolysaccharides of bacterial cell walls, and for blood group substances and other glycopro...<br/>Year introduced: 1991(1975)

MeSH
Profile neighbors for GEO Profiles (Select 132556259) (92)
GEO Profiles
High and low chromosomal instability phenotypes in stage II and III colorectal c...
High and low chromosomal instability phenotypes in stage II and III colorectal cancers
Accession: GDS4380

GEO DataSets
Related DataSets for GEO Profiles (Select 85053962) (1)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001488516	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 12, 2020)	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

SCV001488516

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 12, 2020)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001488516.4

#	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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glycine at codon 366 of the RAD50 protein (p.Ala366Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine.

#	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

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