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NM_000051.4(ATM):c.4098_4099del (p.Cys1366_Asp1367delinsTer) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 29, 2022
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:
RCV000221878.7

Allele description [Variation Report for NM_000051.4(ATM):c.4098_4099del (p.Cys1366_Asp1367delinsTer)]

NM_000051.4(ATM):c.4098_4099del (p.Cys1366_Asp1367delinsTer)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.4098_4099del (p.Cys1366_Asp1367delinsTer)
Other names:
p.Cys1366Ter
HGVS:
  • NC_000011.10:g.108287702TG[1]
  • NG_009830.1:g.69871TG[1]
  • NM_000051.4:c.4098_4099delMANE SELECT
  • NM_001351834.2:c.4098_4099del
  • NP_000042.3:p.Cys1366_Asp1367delinsTer
  • NP_001338763.1:p.Cys1366_Asp1367delinsTer
  • LRG_135t1:c.4098_4099del
  • LRG_135:g.69871TG[1]
  • NC_000011.9:g.108158429TG[1]
  • NC_000011.9:g.108158429_108158430del
  • NM_000051.3:c.4098_4099del
  • NM_000051.3:c.4098_4099delTG
Links:
dbSNP: rs876658248
NCBI 1000 Genomes Browser:
rs876658248
Molecular consequence:
  • NM_000051.4:c.4098_4099del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.4098_4099del - nonsense - [Sequence Ontology: SO:0001587]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000273245Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 29, 2022) 		germlineclinical testing

Citation Link,

SCV000682185Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 15, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000273245.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.4098_4099delTG pathogenic mutation, located in coding exon 26 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 4098 to 4099, causing a translational frameshift with a predicted alternate stop codon (p.C1366*). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000682185.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant deletes 2 nucleotides in exon 27 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024