NM_000051.4(ATM):c.5549del (p.Leu1850fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000219889.4

Allele description [Variation Report for NM_000051.4(ATM):c.5549del (p.Leu1850fs)]

NM_000051.4(ATM):c.5549del (p.Leu1850fs)

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.5549del (p.Leu1850fs)
HGVS:
  • NC_000011.10:g.108304727del
  • NG_009830.1:g.86896del
  • NM_000051.4:c.5549delMANE SELECT
  • NM_001351834.2:c.5549del
  • NP_000042.3:p.Leu1850fs
  • NP_000042.3:p.Leu1850fs
  • NP_001338763.1:p.Leu1850fs
  • LRG_135t1:c.5549del
  • LRG_135:g.86896del
  • LRG_135p1:p.Leu1850fs
  • NC_000011.9:g.108175451del
  • NC_000011.9:g.108175454del
  • NM_000051.3:c.5549del
  • NM_000051.3:c.5549delT
Protein change:
L1850fs
Links:
dbSNP: rs876658287
NCBI 1000 Genomes Browser:
rs876658287
Molecular consequence:
  • NM_000051.4:c.5549del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.5549del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000273322Ambry Geneticscriteria provided, single submitter
Pathogenic
(Mar 20, 2018)
germlineclinical testing

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

Citation Link,

SCV001344865Color Health, Inccriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

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

Description

This variant deletes 1 nucleotide in exon 37 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.

SCV001344865

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

New mutations, polymorphisms, and rare variants in the ATM gene detected by a novel SSCP strategy.

CastellvĂ­-Bel S, Sheikhavandi S, Telatar M, Tai LQ, Hwang M, Wang Z, Yang Z, Cheng R, Gatti RA.

Hum Mutat. 1999;14(2):156-62.

PubMed [citation]
PMID:
10425038

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
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000273322.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The c.5549delT pathogenic mutation, located in coding exon 36 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 5549, causing a translational frameshift with a predicted alternate stop codon. This alteration has been reported in multiple individuals with Ataxia-Telangiectasia (Sandoval N et al, Hum. Mol. Genet. 1999 Jan; 8(1):69-79; Li A et al, Am. J. Med. Genet. 2000 May; 92(3):170-7; Castellví-Bel S et al, Hum. Mutat. 1999; 14(2):156-62). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001344865.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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