NM_000051.4(ATM):c.7998dup (p.Met2667fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: May 14, 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:
RCV000115259.7

Allele description [Variation Report for NM_000051.4(ATM):c.7998dup (p.Met2667fs)]

NM_000051.4(ATM):c.7998dup (p.Met2667fs)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
Duplication
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.7998dup (p.Met2667fs)
HGVS:
  • NC_000011.10:g.108333956dup
  • NG_009830.1:g.116125dup
  • NG_054724.1:g.140877dup
  • NM_000051.4:c.7998dupMANE SELECT
  • NM_001330368.2:c.641-24885dup
  • NM_001351110.2:c.*38+1264dup
  • NM_001351834.2:c.7998dup
  • NP_000042.3:p.Met2667fs
  • NP_001338763.1:p.Met2667fs
  • LRG_135t1:c.7998dup
  • LRG_135:g.116125dup
  • NC_000011.9:g.108204683dup
  • NM_000051.3:c.7998dup
  • NM_000051.3:c.7998dupT
  • p.M2667Yfs*4
  • p.M2667YfsX4
Protein change:
M2667fs
Links:
dbSNP: rs587779869
NCBI 1000 Genomes Browser:
rs587779869
Molecular consequence:
  • NM_000051.4:c.7998dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.7998dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330368.2:c.641-24885dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+1264dup - intron variant - [Sequence Ontology: SO:0001627]
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
SCV000185259Ambry Geneticscriteria provided, single submitter
Pathogenic
(Nov 26, 2013)
germlineclinical testing

Citation Link,

SCV000682448Color Health, Inccriteria provided, single submitter
Pathogenic
(May 14, 2020)
germlineclinical testing

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

Description

This variant inserts 1 nucleotide in exon 54 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. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.

SCV000682448

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, SCV000185259.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

​The c.7998dupT pathogenic mutation, located in coding exon 53 of the ATM gene, results from a duplication of T at position 7998, 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, SCV000682448.2

#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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