NM_000051.4(ATM):c.4664del (p.Leu1555fs) 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:
RCV000214193.2

Allele description [Variation Report for NM_000051.4(ATM):c.4664del (p.Leu1555fs)]

NM_000051.4(ATM):c.4664del (p.Leu1555fs)

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.4664del (p.Leu1555fs)
HGVS:
  • NC_000011.10:g.108293365del
  • NG_009830.1:g.75534del
  • NM_000051.3:c.4664del
  • NM_000051.4:c.4664delMANE SELECT
  • NM_001351834.2:c.4664del
  • NP_000042.3:p.Leu1555fs
  • NP_000042.3:p.Leu1555fs
  • NP_001338763.1:p.Leu1555fs
  • LRG_135t1:c.4664del
  • LRG_135:g.75534del
  • LRG_135p1:p.Leu1555fs
  • NC_000011.9:g.108164092del
  • NM_000051.3:c.4664delT
Protein change:
L1555fs
Links:
dbSNP: rs876659039
NCBI 1000 Genomes Browser:
rs876659039
Molecular consequence:
  • NM_000051.3:c.4664del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000051.4:c.4664del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.4664del - 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
SCV000275009Ambry Geneticscriteria provided, single submitter
Pathogenic
(Apr 7, 2015)
germlineclinical testing

Citation Link,

SCV001350121Color 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 31 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.

SCV001350121

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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, SCV000275009.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.4664delT pathogenic mutation, located in coding exon 30 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 4664, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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

From Color Health, Inc, SCV001350121.1

#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: Nov 27, 2021

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