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NM_000051.4(ATM):c.6392C>A (p.Ala2131Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 16, 2023
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:
RCV000570727.15

Allele description [Variation Report for NM_000051.4(ATM):c.6392C>A (p.Ala2131Asp)]

NM_000051.4(ATM):c.6392C>A (p.Ala2131Asp)

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.6392C>A (p.Ala2131Asp)
HGVS:
  • NC_000011.10:g.108319998C>A
  • NG_009830.1:g.102167C>A
  • NG_054724.1:g.154835G>T
  • NM_000051.4:c.6392C>AMANE SELECT
  • NM_001330368.2:c.641-10927G>T
  • NM_001351110.2:c.*39-10927G>T
  • NM_001351834.2:c.6392C>A
  • NP_000042.3:p.Ala2131Asp
  • NP_000042.3:p.Ala2131Asp
  • NP_001338763.1:p.Ala2131Asp
  • LRG_135t1:c.6392C>A
  • LRG_135:g.102167C>A
  • LRG_135p1:p.Ala2131Asp
  • NC_000011.9:g.108190725C>A
  • NM_000051.3:c.6392C>A
Protein change:
A2131D
Links:
dbSNP: rs1060501594
NCBI 1000 Genomes Browser:
rs1060501594
Molecular consequence:
  • NM_001330368.2:c.641-10927G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-10927G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6392C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.6392C>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000668119Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Apr 16, 2023) 		germlineclinical testing

Citation Link,

SCV001357051Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 27, 2022) 		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

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, SCV000668119.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.A2131D variant (also known as c.6392C>A), located in coding exon 43 of the ATM gene, results from a C to A substitution at nucleotide position 6392. The alanine at codon 2131 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Color Diagnostics, LLC DBA Color Health, SCV001357051.2

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

Description

This missense variant replaces alanine with aspartic acid at codon 2131 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 26, 2024