NM_000051.3(ATM):c.1607+1G>T AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 16, 2015)

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:
RCV000203930.1

Allele description [Variation Report for NM_000051.3(ATM):c.1607+1G>T]

NM_000051.3(ATM):c.1607+1G>T

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.3(ATM):c.1607+1G>T
HGVS:
  • NC_000011.10:g.108251073G>T
  • NG_009830.1:g.33242G>T
  • NM_000051.3:c.1607+1G>T
  • LRG_135t1:c.1607+1G>T
  • LRG_135:g.33242G>T
  • NC_000011.9:g.108121800G>T
Links:
dbSNP: rs772926890
NCBI 1000 Genomes Browser:
rs772926890
Allele Frequency:
0.00001(T)
Molecular consequence:
  • NM_000051.3:c.1607+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
MedGen: C0004135; Orphanet: 100; OMIM: 208900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000261188Invitaecriteria provided, single submitter
Pathogenic
(Oct 13, 2015)
germlineclinical testing

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

SCV000485314Counsylcriteria provided, single submitter
Likely pathogenic
(Nov 16, 2015)
unknownclinical testing

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

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families.

Chessa L, Piane M, Magliozzi M, Torrente I, Savio C, Lulli P, De Luca A, Dallapiccola B.

Ann Hum Genet. 2009 Sep;73(Pt 5):532-9. doi: 10.1111/j.1469-1809.2009.00535.x.

PubMed [citation]
PMID:
19691550

Details of each submission

From Invitae, SCV000261188.2

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

Description

This sequence change affects a donor splice site in intron 10. Experimental studies have shown that this nucleotide change disrupts mRNA splicing and leads to a loss of ATM protein (PMID: 9450906, 9443866, 23454770). Truncating variants in ATM are known to be pathogenic. This particular truncation has been reported in multiple patients with with ataxia telangiectasia, including one homozygous individual (PMID: 9450906, 9443866, 19691550). This variant is also known as IVS12+1G>T in the literature. For these reasons, this variant has been classified as Pathogenic.

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

From Counsyl, SCV000485314.1

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

Last Updated: Jul 21, 2018