NM_000051.4(ATM):c.689del (p.Asn230fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 6, 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:: RCV001025773.6

Allele description [Variation Report for NM_000051.4(ATM):c.689del (p.Asn230fs)]

NM_000051.4(ATM):c.689del (p.Asn230fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.689del (p.Asn230fs)

HGVS:

NC_000011.10:g.108244814del
NG_009830.1:g.26983del
NM_000051.4:c.689delMANE SELECT
NM_001351834.2:c.689del
NP_000042.3:p.Asn230fs
NP_000042.3:p.Asn230fs
NP_001338763.1:p.Asn230fs
LRG_135t1:c.689del
LRG_135:g.26983del
LRG_135p1:p.Asn230fs
NC_000011.9:g.108115539del
NC_000011.9:g.108115541del
NM_000051.3:c.687delA
NM_000051.3:c.689del
NM_000051.3:c.689del
NM_000051.3:c.689delA
NM_000051.3:c.689delA

Protein change:

N230fs

Links:

dbSNP: rs1057518965

NCBI 1000 Genomes Browser:

rs1057518965

Molecular consequence:

NM_000051.4:c.689del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351834.2:c.689del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Mus musculus 232000009835788 genomic scaffold, whole genome shotgun sequence
Mus musculus 232000009835788 genomic scaffold, whole genome shotgun sequence
gi|74140709|gnl|WGS:AAHY|2320000098 |gb|CH466634.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001188025	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002538561	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely pathogenic (Nov 4, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 12810666, 31050087 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001188025

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 6, 2023)

germline

clinical testing

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

Citation Link,

SCV002538561

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely pathogenic
(Nov 4, 2021)

germline

curation

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Contributions of ATM mutations to familial breast and ovarian cancer.

Thorstenson YR, Roxas A, Kroiss R, Jenkins MA, Yu KM, Bachrich T, Muhr D, Wayne TL, Chu G, Davis RW, Wagner TM, Oefner PJ.

Cancer Res. 2003 Jun 15;63(12):3325-33.

PubMed [citation]

PMID:: 12810666

Functional classification of ATM variants in ataxia-telangiectasia patients.

Fiévet A, Bellanger D, Rieunier G, Dubois d'Enghien C, Sophie J, Calvas P, Carriere JP, Anheim M, Castrioto A, Flabeau O, Degos B, Ewenczyk C, Mahlaoui N, Touzot F, Suarez F, Hully M, Roubertie A, Aladjidi N, Tison F, Antoine-Poirel H, Dahan K, Doummar D, et al.

Hum Mutat. 2019 Oct;40(10):1713-1730. doi: 10.1002/humu.23778. Epub 2019 May 17.

PubMed [citation]

PMID:: 31050087

Details of each submission

From Ambry Genetics, SCV001188025.5

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

Description

The c.689delA pathogenic mutation, located in coding exon 6 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 689, causing a translational frameshift with a predicted alternate stop codon (p.N230Ifs*4). This mutation, designated 687delA, was identified in an Austrian family with three or more affected individuals, including two diagnosed with breast cancer before age 50 (Thorstenson YR et al. Cancer Res. 2003 Jun;63:3325-33). 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002538561.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

#	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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