NM_000051.4(ATM):c.6371_6372insG (p.Tyr2124Ter) AND Malignant tumor of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 13, 2021
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:: RCV001732018.9

Allele description [Variation Report for NM_000051.4(ATM):c.6371_6372insG (p.Tyr2124Ter)]

NM_000051.4(ATM):c.6371_6372insG (p.Tyr2124Ter)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

Insertion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.6371_6372insG (p.Tyr2124Ter)

HGVS:

NC_000011.10:g.108319977_108319978insG
NG_009830.1:g.102146_102147insG
NG_054724.1:g.154855_154856insC
NM_000051.4:c.6371_6372insGMANE SELECT
NM_001330368.2:c.641-10907_641-10906insC
NM_001351110.2:c.*39-10907_*39-10906insC
NM_001351834.2:c.6371_6372insG
NP_000042.3:p.Tyr2124Ter
NP_000042.3:p.Tyr2124Terfs
NP_001338763.1:p.Tyr2124Ter
LRG_135t1:c.6371_6372insG
LRG_135:g.102146_102147insG
LRG_135p1:p.Tyr2124Terfs
NC_000011.9:g.108190704_108190705insG
NM_000051.3:c.6371_6372insG

Protein change:

Y2124*

Links:

dbSNP: rs2085078278

NCBI 1000 Genomes Browser:

rs2085078278

Molecular consequence:

NM_001330368.2:c.641-10907_641-10906insC - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10907_*39-10906insC - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6371_6372insG - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.6371_6372insG - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Malignant tumor of breast
Synonyms:: Malignant breast neoplasm; Cancer breast
Identifiers:: MONDO: MONDO:0007254; MedGen: C0006142

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001983541	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 13, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10817650, 8659541, 8808599 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001983541

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 13, 2021)

germline

clinical testing

PubMed (3)
[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

Citations

PubMed

Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients.

Li A, Swift M.

Am J Med Genet. 2000 May 29;92(3):170-7.

PubMed [citation]

PMID:: 10817650

Ataxia-telangiectasia: mutations in ATM cDNA detected by protein-truncation screening.

Telatar M, Wang Z, Udar N, Liang T, Bernatowska-Matuszkiewicz E, Lavin M, Shiloh Y, Concannon P, Good RA, Gatti RA.

Am J Hum Genet. 1996 Jul;59(1):40-4.

PubMed [citation]

PMID:: 8659541
PMCID:: PMC1915099

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983541.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: ATM c.6371_6372insG (p.Tyr2124X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. Additionally, one functional study reports experimental evidence that this variant results in exon deleted, presumably allowing the production of a shortened, in-frame transcript, which could still have some partial function (Wright_1996). The variant was absent in 249538 control chromosomes (gnomAD). c.6371_6372insG has been reported in the literature in individuals affected with Ataxia-Telangiectasia (Wright_1996, Telatar_1996, Li_2000). These data indicate that the variant may be associated with disease. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Nov 3, 2024

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