NM_000051.4(ATM):c.7269A>C (p.Glu2423Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 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:: RCV004031018.1

Allele description [Variation Report for NM_000051.4(ATM):c.7269A>C (p.Glu2423Asp)]

NM_000051.4(ATM):c.7269A>C (p.Glu2423Asp)

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.7269A>C (p.Glu2423Asp)

HGVS:

NC_000011.10:g.108329200A>C
NG_009830.1:g.111369A>C
NG_054724.1:g.145633T>G
NM_000051.4:c.7269A>CMANE SELECT
NM_001330368.2:c.641-20129T>G
NM_001351110.2:c.*38+6020T>G
NM_001351834.2:c.7269A>C
NP_000042.3:p.Glu2423Asp
NP_000042.3:p.Glu2423Asp
NP_001338763.1:p.Glu2423Asp
LRG_135t1:c.7269A>C
LRG_135:g.111369A>C
LRG_135p1:p.Glu2423Asp
NC_000011.9:g.108199927A>C
NC_000011.9:g.108199927A>C
NM_000051.3:c.7269A>C

Protein change:

E2423D

Links:

dbSNP: rs864622471

NCBI 1000 Genomes Browser:

rs864622471

Molecular consequence:

NM_001330368.2:c.641-20129T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+6020T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7269A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7269A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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hypothetical protein SPRG_04703 [Saprolegnia parasitica CBS 223.65]
hypothetical protein SPRG_04703 [Saprolegnia parasitica CBS 223.65]
gi|813135464|ref|XP_012198499.1||gn _WGS:ADCG|SPRG_04703T0

Protein
uncharacterized protein NGA_0649500, partial [Nannochloropsis gaditana CCMP526]
uncharacterized protein NGA_0649500, partial [Nannochloropsis gaditana CCMP526]
gi|553192929|ref|XP_005855673.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005019996	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005019996

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 14, 2023)

germline

clinical testing

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

Citation Link

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

Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

Decker B, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Ahmed S, Baynes C, Conroy DM, Brown J, Luben R, Ostrander EA, Pharoah PD, Dunning AM, Easton DF.

J Med Genet. 2017 Nov;54(11):732-741. doi: 10.1136/jmedgenet-2017-104588. Epub 2017 Aug 4.

PubMed [citation]

PMID:: 28779002
PMCID:: PMC5740532

Details of each submission

From Ambry Genetics, SCV005019996.1

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

Description

The p.E2423D variant (also known as c.7269A>C), located in coding exon 48 of the ATM gene, results from an A to C substitution at nucleotide position 7269. A different alteration resulting in the same amino acid change (c.7269A>T, p.E2423D) was identified in 1 of 13087 breast cancer cases and was not observed in 5488 control individuals in the UK (Decker B et al. J Med Genet, 2017 Nov;54:732-741). The glutamic acid at codon 2423 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Oct 20, 2024

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