NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 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:: RCV000159761.7

Allele description [Variation Report for NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter)]

NM_000051.4(ATM):c.3049C>T (p.Gln1017Ter)

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.3049C>T (p.Gln1017Ter)

Other names:

p.Q1017*:CAG>TAG

HGVS:

NC_000011.10:g.108271378C>T
NG_009830.1:g.53547C>T
NM_000051.4:c.3049C>TMANE SELECT
NM_001351834.2:c.3049C>T
NP_000042.3:p.Gln1017Ter
NP_000042.3:p.Gln1017Ter
NP_001338763.1:p.Gln1017Ter
LRG_135t1:c.3049C>T
LRG_135:g.53547C>T
LRG_135p1:p.Gln1017Ter
NC_000011.9:g.108142105C>T
NM_000051.3:c.3049C>T
p.Q1017*

Protein change:

Q1017*

Links:

dbSNP: rs730881388

NCBI 1000 Genomes Browser:

rs730881388

Molecular consequence:

NM_000051.4:c.3049C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.3049C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000216002	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Aug 6, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002535289	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely pathogenic (Dec 11, 2021)	germline	curation	PubMed (4) [See all records that cite these PMIDs] 26681312, 34377931, 31447099, 31050087 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000216002

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Aug 6, 2021)

germline

clinical testing

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

Citation Link,

SCV002535289

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely pathogenic
(Dec 11, 2021)

germline

curation

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing, curation

Citations

PubMed

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

Penetrance of Breast Cancer Susceptibility Genes From the eMERGE III Network.

Fan X, Wynn J, Shang N, Liu C, Fedotov A, Hallquist MLG, Buchanan AH, Williams MS, Smith ME, Hoell C, Rasmussen-Torvik LJ, Peterson JF, Wiesner GL, Murad AM, Jarvik GP, Gordon AS, Rosenthal EA, Stanaway IB, Crosslin DR, Larson EB, Leppig KA, Henrikson NB, et al.

JNCI Cancer Spectr. 2021 Aug;5(4). doi: 10.1093/jncics/pkab044.

PubMed [citation]

PMID:: 34377931
PMCID:: PMC8346699

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000216002.6

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

Description

The p.Q1017* pathogenic mutation (also known as c.3049C>T), located in coding exon 19 of the ATM gene, results from a C to T substitution at nucleotide position 3049. This changes the amino acid from a glutamine to a stop codon within coding exon 19. This alteration was identified in 1/10030 consecutive patients referred for evaluation by an NGS hereditary cancer panel (Susswein LR et al. Genet. Med., 2016 08;18:823-32). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

From Sema4, Sema4, SCV002535289.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (4)

#	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: Feb 28, 2024

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