NM_000051.4(ATM):c.7880del (p.Tyr2627fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Nov 4, 2019)

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:
RCV001026909.2

Allele description [Variation Report for NM_000051.4(ATM):c.7880del (p.Tyr2627fs)]

NM_000051.4(ATM):c.7880del (p.Tyr2627fs)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
Deletion
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.7880del (p.Tyr2627fs)
HGVS:
  • NC_000011.10:g.108332853del
  • NG_009830.1:g.115022del
  • NG_054724.1:g.141980del
  • NM_000051.4:c.7880delMANE SELECT
  • NM_001330368.2:c.641-23782del
  • NM_001351110.2:c.*38+2367del
  • NM_001351834.2:c.7880del
  • NP_000042.3:p.Tyr2627fs
  • NP_001338763.1:p.Tyr2627fs
  • LRG_135t1:c.7880del
  • LRG_135:g.115022del
  • NC_000011.9:g.108203580del
  • NM_000051.3:c.7880del
  • NM_000051.3:c.7880delA
Protein change:
Y2627fs
Links:
dbSNP: rs1057516599
NCBI 1000 Genomes Browser:
rs1057516599
Molecular consequence:
  • NM_000051.4:c.7880del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.7880del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330368.2:c.641-23782del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+2367del - 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
SCV001189383Ambry Geneticscriteria provided, single submitter
Pathogenic
(Apr 30, 2018)
germlineclinical testing

Citation Link,

SCV001340191Color Health, Inccriteria provided, single submitter
Pathogenic
(Nov 4, 2019)
germlineclinical testing

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

Description

This variant deletes 1 nucleotide in exon 53 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. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250804 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.

SCV001340191

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, SCV001189383.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.7880delA pathogenic mutation, located in coding exon 52 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 7880, causing a translational frameshift with a predicted alternate stop codon (p.Y2627Lfs*4). 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, SCV001340191.1

#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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