NM_000051.4(ATM):c.2606C>G (p.Ala869Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 20, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000164332.12

Allele description [Variation Report for NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)]

NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)

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.2606C>G (p.Ala869Gly)

Other names:

NP_000042.3:p.Ala869Gly

HGVS:

NC_000011.10:g.108267310C>G
NG_009830.1:g.49479C>G
NM_000051.4:c.2606C>GMANE SELECT
NM_001351834.2:c.2606C>G
NP_000042.3:p.Ala869Gly
NP_000042.3:p.Ala869Gly
NP_001338763.1:p.Ala869Gly
LRG_135t1:c.2606C>G
LRG_135:g.49479C>G
LRG_135p1:p.Ala869Gly
NC_000011.9:g.108138037C>G
NM_000051.3:c.2606C>G
p.A869G

Protein change:

A869G

Links:

dbSNP: rs145513717

NCBI 1000 Genomes Browser:

rs145513717

Molecular consequence:

NM_000051.4:c.2606C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2606C>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000214963	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 20, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000911326	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 3, 2017)	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

SCV000214963

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 20, 2022)

germline

clinical testing

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

Citation Link,

SCV000911326

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jan 3, 2017)

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

Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.

Chaffee KG, Oberg AL, McWilliams RR, Majithia N, Allen BA, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Petersen GM.

Genet Med. 2018 Jan;20(1):119-127. doi: 10.1038/gim.2017.85. Epub 2017 Jul 20.

PubMed [citation]

PMID:: 28726808
PMCID:: PMC5760284

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000214963.9

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

Description

The p.A869G variant (also known as c.2606C>G), located in coding exon 16 of the ATM gene, results from a C to G substitution at nucleotide position 2606. The alanine at codon 869 is replaced by glycine, an amino acid with similar properties. This variant has been identified in an individual with pancreatic cancer (Chaffee KG et al. Genet Med, 2018 01;20:119-127). This amino acid position is not well 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

From Color Diagnostics, LLC DBA Color Health, SCV000911326.1

#	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: Sep 29, 2024

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