NM_000051.4(ATM):c.2377_2378dup (p.Ser794fs) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Sep 16, 2016)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000410884.1

Allele description [Variation Report for NM_000051.4(ATM):c.2377_2378dup (p.Ser794fs)]

NM_000051.4(ATM):c.2377_2378dup (p.Ser794fs)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.2377_2378dup (p.Ser794fs)
HGVS:
  • NC_000011.10:g.108258986_108258987dup
  • NG_009830.1:g.41155_41156dup
  • NM_000051.4:c.2377_2378dupMANE SELECT
  • NM_001351834.2:c.2377_2378dup
  • NP_000042.3:p.Ser794fs
  • NP_001338763.1:p.Ser794fs
  • LRG_135:g.41155_41156dup
  • NC_000011.9:g.108129713_108129714dup
  • NM_000051.3:c.2377_2378dupAA
Protein change:
S794fs
Links:
dbSNP: rs1057516980
NCBI 1000 Genomes Browser:
rs1057516980
Molecular consequence:
  • NM_000051.4:c.2377_2378dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001351834.2:c.2377_2378dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000486540Counsylcriteria provided, single submitter
Likely pathogenic
(Sep 16, 2016)
unknownclinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000547053Invitaecriteria provided, single submitter
Pathogenic
(Mar 31, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Counsyl, SCV000486540.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000547053.2

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

Description

This sequence change inserts 2 nucleotides in exon 16 of the ATM mRNA (c.2377_2378dupAA), causing a frameshift at codon 794. This creates a premature translational stop signal (p.Ser794Argfs*15) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in ATM are known to be pathogenic (PMID: 10817650, 19781682). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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