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NM_000051.4(ATM):c.6257A>T (p.Tyr2086Phe) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 10, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001731490.10

Allele description [Variation Report for NM_000051.4(ATM):c.6257A>T (p.Tyr2086Phe)]

NM_000051.4(ATM):c.6257A>T (p.Tyr2086Phe)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.6257A>T (p.Tyr2086Phe)
Other names:
p.Y2086F:TAT>TTT
HGVS:
  • NC_000011.10:g.108317431A>T
  • NG_009830.1:g.99600A>T
  • NG_054724.1:g.157402T>A
  • NM_000051.4:c.6257A>TMANE SELECT
  • NM_001330368.2:c.641-8360T>A
  • NM_001351110.2:c.*39-8360T>A
  • NM_001351834.2:c.6257A>T
  • NP_000042.3:p.Tyr2086Phe
  • NP_000042.3:p.Tyr2086Phe
  • NP_001338763.1:p.Tyr2086Phe
  • LRG_135t1:c.6257A>T
  • LRG_135:g.99600A>T
  • LRG_135p1:p.Tyr2086Phe
  • NC_000011.9:g.108188158A>T
  • NM_000051.3:c.6257A>T
Protein change:
Y2086F
Links:
dbSNP: rs730881380
NCBI 1000 Genomes Browser:
rs730881380
Molecular consequence:
  • NM_001330368.2:c.641-8360T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-8360T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6257A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.6257A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001983533Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Nov 10, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer.

Hauke J, Horvath J, Groß E, Gehrig A, Honisch E, Hackmann K, Schmidt G, Arnold N, Faust U, Sutter C, Hentschel J, Wang-Gohrke S, Smogavec M, Weber BHF, Weber-Lassalle N, Weber-Lassalle K, Borde J, Ernst C, Altmüller J, Volk AE, Thiele H, Hübbel V, et al.

Cancer Med. 2018 Apr;7(4):1349-1358. doi: 10.1002/cam4.1376. Epub 2018 Mar 9.

PubMed [citation]
PMID:
29522266
PMCID:
PMC5911592

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium, Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]
PMID:
33471991
PMCID:
PMC7611105
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983533.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: ATM c.6257A>T (p.Tyr2086Phe) results in a conservative amino acid change located in the PIK-related kinase domain (IPR014009) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 365040 control chromosomes (gnomAD, Dorling_2021, Karlsson_2021). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6257A>T has been reported in the literature in individuals with a personal or family history of cancer (e.g., Hauke_2018, Dorling_2021, Bhai_2021, deOliveira-Garcia_2022), but it was also reported in unaffected controls (e.g., Dorling_2021, Karlsson_2021). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33471991, 29522266, 33436325, 34326862, 35181726). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Feb 8, 2025