NM_000051.4(ATM):c.1855A>C (p.Asn619His) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jun 28, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001530924.1

Allele description [Variation Report for NM_000051.4(ATM):c.1855A>C (p.Asn619His)]

NM_000051.4(ATM):c.1855A>C (p.Asn619His)

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.1855A>C (p.Asn619His)
HGVS:
  • NC_000011.10:g.108252869A>C
  • NG_009830.1:g.35038A>C
  • NM_000051.3:c.1855A>C
  • NM_000051.4:c.1855A>CMANE SELECT
  • NM_001351834.2:c.1855A>C
  • NP_000042.3:p.Asn619His
  • NP_000042.3:p.Asn619His
  • NP_001338763.1:p.Asn619His
  • LRG_135t1:c.1855A>C
  • LRG_135:g.35038A>C
  • LRG_135p1:p.Asn619His
  • NC_000011.9:g.108123596A>C
  • p.N619H
Protein change:
N619H
Links:
dbSNP: rs140882609
NCBI 1000 Genomes Browser:
rs140882609
Molecular consequence:
  • NM_000051.3:c.1855A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.1855A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.1855A>C - 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
SCV000694201Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jun 28, 2021)
germlineclinical testing

PubMed (2)
[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

Identification of potential therapeutic targets by molecular profiling of 628 cases of uterine serous carcinoma.

Jones NL, Xiu J, Reddy SK, Burke WM, Tergas AI, Wright JD, Hou JY.

Gynecol Oncol. 2015 Sep;138(3):620-6. doi: 10.1016/j.ygyno.2015.06.034. Epub 2015 Jun 26.

PubMed [citation]
PMID:
26123645

Rare germline variants in ATM are associated with chronic lymphocytic leukemia.

Tiao G, Improgo MR, Kasar S, Poh W, Kamburov A, Landau DA, Tausch E, Taylor-Weiner A, Cibulskis C, Bahl S, Fernandes SM, Hoang K, Rheinbay E, Kim HT, Bahlo J, Robrecht S, Fischer K, Hallek M, Gabriel S, Lander ES, Stilgenbauer S, Wu CJ, et al.

Leukemia. 2017 Oct;31(10):2244-2247. doi: 10.1038/leu.2017.201. Epub 2017 Jun 27. No abstract available.

PubMed [citation]
PMID:
28652578
PMCID:
PMC5628120

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694201.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: ATM c.1855A>C (p.Asn619His) results in a conservative amino acid change in the encoded protein sequence. Five 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 250960 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1855A>C has been previously reported in one uterine serous carcinoma sample without confirmation of its origin (germline vs somatic) (Jones_2015) and a CLL patient (Tiao_2017). These reports do not provide unequivocal conclusions about association of the variant with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as uncertain significance (n=3) and likely benign (n=1). 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: Nov 27, 2021

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