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NM_139027.6(ADAMTS13):c.3044+1G>A AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Aug 17, 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:
RCV000435056.3

Allele description [Variation Report for NM_139027.6(ADAMTS13):c.3044+1G>A]

NM_139027.6(ADAMTS13):c.3044+1G>A

Gene:
ADAMTS13:ADAM metallopeptidase with thrombospondin type 1 motif 13 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.2
Genomic location:
Preferred name:
NM_139027.6(ADAMTS13):c.3044+1G>A
HGVS:
  • NC_000009.12:g.133449966G>A
  • NG_011934.2:g.40628G>A
  • NM_139025.5:c.3044+1G>A
  • NM_139026.6:c.2951+1G>A
  • NM_139027.6:c.3044+1G>AMANE SELECT
  • LRG_544:g.40628G>A
  • NC_000009.11:g.136315087G>A
  • NM_139025.3:c.3044+1G>A
Links:
dbSNP: rs1057520680
NCBI 1000 Genomes Browser:
rs1057520680
Molecular consequence:
  • NM_139025.5:c.3044+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_139026.6:c.2951+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_139027.6:c.3044+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000516940GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Apr 28, 2015) 		germlineclinical testing

Citation Link,

SCV004316788Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 17, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.

Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM.

Nature. 2001 Oct 4;413(6855):488-94.

PubMed [citation]
PMID:
11586351
See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000516940.3

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

Description

The c.3044+1G>A variant in the ADAMTS13 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This splice site variant destroys the canonicalsplice donor site in intron 23. It is predicted to cause abnormal gene splicing, either leading to an abnormalmessage that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the messageis used for protein translation. The c.3044+1G>A variant was not observed in approximately 6500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating itis not a common benign variant in these populations. We interpret c.3044+1G>A as a pathogenic variant.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004316788.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 379656). This variant has not been reported in the literature in individuals affected with ADAMTS13-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 23 of the ADAMTS13 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ADAMTS13 are known to be pathogenic (PMID: 11586351, 12753286, 21781265).

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

Last Updated: Sep 29, 2024