NM_000051.4(ATM):c.8428A>C (p.Lys2810Gln) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 17, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001526890.11

Allele description [Variation Report for NM_000051.4(ATM):c.8428A>C (p.Lys2810Gln)]

NM_000051.4(ATM):c.8428A>C (p.Lys2810Gln)

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.8428A>C (p.Lys2810Gln)

Other names:

p.K2810Q:AAA>CAA

HGVS:

NC_000011.10:g.108345752A>C
NG_009830.1:g.127921A>C
NG_054724.1:g.129081T>G
NM_000051.4:c.8428A>CMANE SELECT
NM_001330368.2:c.641-36681T>G
NM_001351110.2:c.695-10460T>G
NM_001351834.2:c.8428A>C
NP_000042.3:p.Lys2810Gln
NP_000042.3:p.Lys2810Gln
NP_001338763.1:p.Lys2810Gln
LRG_135t1:c.8428A>C
LRG_135:g.127921A>C
LRG_135p1:p.Lys2810Gln
NC_000011.9:g.108216479A>C
NM_000051.3:c.8428A>C

Protein change:

K2810Q

Links:

dbSNP: rs730881325

NCBI 1000 Genomes Browser:

rs730881325

Molecular consequence:

NM_001330368.2:c.641-36681T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.695-10460T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.8428A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.8428A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001737636	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 17, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31159747, 33436325 Citation Link,
SCV004242558	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 6, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001737636

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 17, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV004242558

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 6, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]

PMID:: 31159747
PMCID:: PMC6547505

Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.

Karlsson Q, Brook MN, Dadaev T, Wakerell S, Saunders EJ, Muir K, Neal DE, Giles GG, MacInnis RJ, Thibodeau SN, McDonnell SK, Cannon-Albright L, Teixeira MR, Paulo P, Cardoso M, Huff C, Li D, Yao Y, Scheet P, Permuth JB, Stanford JL, Dai JY, et al.

Eur Urol Oncol. 2021 Aug;4(4):570-579. doi: 10.1016/j.euo.2020.12.001. Epub 2021 Jan 9.

PubMed [citation]

PMID:: 33436325
PMCID:: PMC8381233

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737636.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: ATM c.8428A>C (p.Lys2810Gln) results in a conservative amino acid change located in the Phosphatidylinositol 3-/4-kinase, catalytic domain (IPR000403) 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 4e-05 in 250508 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ATM causing Ataxia-Telangiectasia (4e-05 vs 0.004), allowing no conclusion about variant significance. c.8428A>C has been reported in the literature in individuals undergoing multigene panel testing for hereditary cancers (example, Tsaousis_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. 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: 31159747, 33436325). ClinVar contains an entry for this variant (Variation ID: 181898). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004242558.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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