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NM_000051.4(ATM):c.7835G>A (p.Arg2612Lys) AND Ataxia-telangiectasia syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 8, 2021
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:
RCV000456297.13

Allele description [Variation Report for NM_000051.4(ATM):c.7835G>A (p.Arg2612Lys)]

NM_000051.4(ATM):c.7835G>A (p.Arg2612Lys)

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.7835G>A (p.Arg2612Lys)
HGVS:
  • NC_000011.10:g.108332808G>A
  • NG_009830.1:g.114977G>A
  • NG_054724.1:g.142025C>T
  • NM_000051.4:c.7835G>AMANE SELECT
  • NM_001330368.2:c.641-23737C>T
  • NM_001351110.2:c.*38+2412C>T
  • NM_001351834.2:c.7835G>A
  • NP_000042.3:p.Arg2612Lys
  • NP_000042.3:p.Arg2612Lys
  • NP_001338763.1:p.Arg2612Lys
  • LRG_135t1:c.7835G>A
  • LRG_135:g.114977G>A
  • LRG_135p1:p.Arg2612Lys
  • NC_000011.9:g.108203535G>A
  • NM_000051.3:c.7835G>A
Protein change:
R2612K
Links:
dbSNP: rs138048269
NCBI 1000 Genomes Browser:
rs138048269
Molecular consequence:
  • NM_001330368.2:c.641-23737C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+2412C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7835G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.7835G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000546819Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 8, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000546819.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs138048269, ExAC 0.002%). This sequence change replaces arginine with lysine at codon 2612 of the ATM protein (p.Arg2612Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine.

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

Last Updated: Nov 3, 2024