NM_000051.4(ATM):c.8151G>A (p.Lys2717=) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Jul 1, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001027230.2

Allele description [Variation Report for NM_000051.4(ATM):c.8151G>A (p.Lys2717=)]

NM_000051.4(ATM):c.8151G>A (p.Lys2717=)

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.8151G>A (p.Lys2717=)
HGVS:
  • NC_000011.10:g.108335109G>A
  • NG_009830.1:g.117278G>A
  • NG_054724.1:g.139724C>T
  • NM_000051.4:c.8151G>AMANE SELECT
  • NM_001330368.2:c.641-26038C>T
  • NM_001351110.2:c.*38+111C>T
  • NM_001351834.2:c.8151G>A
  • NP_000042.3:p.Lys2717=
  • NP_001338763.1:p.Lys2717=
  • LRG_135t1:c.8151G>A
  • LRG_135:g.117278G>A
  • NC_000011.9:g.108205836G>A
  • NM_000051.3:c.8151G>A
Links:
dbSNP: rs1591192550
NCBI 1000 Genomes Browser:
rs1591192550
Molecular consequence:
  • NM_001330368.2:c.641-26038C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+111C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.8151G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001351834.2:c.8151G>A - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001189748Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Jul 1, 2019)
germlineclinical testing

Citation Link,

SCV001342031Color Health, Inccriteria provided, single submitter
Uncertain significance
(Jun 19, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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, SCV001189748.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.8151G>A variant (also known as p.K2717K), located in coding exon 54 of the ATM gene, results from a G to A substitution at nucleotide position 8151. This nucleotide substitution does not change the amino acid at codon 2717. However, this change occurs in the last base pair of coding exon 54, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001342031.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 7, 2021

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