NM_000051.4(ATM):c.194A>G (p.Gln65Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 2024
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:: RCV000567749.3

Allele description [Variation Report for NM_000051.4(ATM):c.194A>G (p.Gln65Arg)]

NM_000051.4(ATM):c.194A>G (p.Gln65Arg)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.194A>G (p.Gln65Arg)

HGVS:

NC_000011.10:g.108229186A>G
NG_009830.1:g.11355A>G
NM_000051.4:c.194A>GMANE SELECT
NM_001351834.2:c.194A>G
NM_001351835.2:c.194A>G
NM_001351836.2:c.194A>G
NP_000042.3:p.Gln65Arg
NP_000042.3:p.Gln65Arg
NP_001338763.1:p.Gln65Arg
NP_001338764.1:p.Gln65Arg
NP_001338765.1:p.Gln65Arg
LRG_135t1:c.194A>G
LRG_135:g.11355A>G
LRG_135p1:p.Gln65Arg
NC_000011.9:g.108099913A>G
NM_000051.3:c.194A>G

Protein change:

Q65R

Links:

dbSNP: rs760471526

NCBI 1000 Genomes Browser:

rs760471526

Molecular consequence:

NM_000051.4:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351835.2:c.194A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351836.2:c.194A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000665376	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000665376

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 22, 2024)

germline

clinical testing

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

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

Pathogenic Variants in Cancer Predisposition Genes and Prostate Cancer Risk in Men of African Ancestry.

Matejcic M, Patel Y, Lilyquist J, Hu C, Lee KY, Gnanaolivu RD, Hart SN, Polley EC, Yadav S, Boddicker NJ, Samara R, Xia L, Sheng X, Lubmawa A, Kiddu V, Masaba B, Namuguzi D, Mutema G, Job K, Henry DM, Ingles SA, Wilkens L, et al.

JCO Precis Oncol. 2020;4:32-43. doi: 10.1200/po.19.00179. Epub 2020 Jan 31.

PubMed [citation]

PMID:: 32832836
PMCID:: PMC7442213

Details of each submission

From Ambry Genetics, SCV000665376.5

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

Description

The p.Q65R variant (also known as c.194A>G), located in coding exon 3 of the ATM gene, results from an A to G substitution at nucleotide position 194. The glutamine at codon 65 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified in a cohort of 3,579 African males diagnosed with prostate cancer who underwent multi-gene panel testing (Matejcic M et al. JCO Precis Oncol, 2020 Jan;4:32-43). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: May 7, 2024

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