NM_000051.4(ATM):c.2873A>G (p.Glu958Gly) AND Malignant tumor of breast

Clinical significance:Uncertain significance

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001355117.1

Allele description [Variation Report for NM_000051.4(ATM):c.2873A>G (p.Glu958Gly)]

NM_000051.4(ATM):c.2873A>G (p.Glu958Gly)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.2873A>G (p.Glu958Gly)
Other names:
p.E958G:GAG>GGG
HGVS:
  • NC_000011.10:g.108271098A>G
  • NG_009830.1:g.53267A>G
  • NM_000051.4:c.2873A>GMANE SELECT
  • NM_001351834.2:c.2873A>G
  • NP_000042.3:p.Glu958Gly
  • NP_000042.3:p.Glu958Gly
  • NP_001338763.1:p.Glu958Gly
  • LRG_135t1:c.2873A>G
  • LRG_135:g.53267A>G
  • LRG_135p1:p.Glu958Gly
  • NC_000011.9:g.108141825A>G
  • NM_000051.3:c.2873A>G
  • p.E958G
Protein change:
E958G
Links:
dbSNP: rs587778069
NCBI 1000 Genomes Browser:
rs587778069
Molecular consequence:
  • NM_000051.4:c.2873A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.2873A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Malignant tumor of breast
Synonyms:
Breast cancer; Malignant breast neoplasm
Identifiers:
MONDO: MONDO:0007254; MedGen: C0006142

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001549906Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001549906.1

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

Description

The ATM p.Glu958Gly variant was identified in 2 of 2020 proband chromosomes (frequency: 0.001) from individuals or families with hereditary breast and ovarian cancer and was present in 1 of 4362 control chromosomes (frequency: 0.0002) from healthy individuals (Bodian 2014, Singh 2017). The variant was also identified in dbSNP (ID: rs587778069) as "With Uncertain Significance allele" and in the ClinVar (5x as Uncertain significance by Invitae, Ambry Genetics, GeneDx and two other submitters) database. The variant was not identified in LOVD 3.0 database. It was identified in control databases in 24 of 246208 chromosomes at a frequency of 0.0001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 33580 chromosomes (freq: 0.00003), European in 1 of 111676 chromosomes (freq: 0.000009), and South Asian in 22 of 30780 chromosomes (freq: 0.0007), while the variant was not observed in the African, Other, Ashkenazi Jewish, East Asian or Finnish populations. The p.Glu958 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: Dec 4, 2021

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