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NM_014319.5(LEMD3):c.2023+1G>A AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 14, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001998570.3

Allele description [Variation Report for NM_014319.5(LEMD3):c.2023+1G>A]

NM_014319.5(LEMD3):c.2023+1G>A

Gene:
LEMD3:LEM domain containing 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q14.3
Genomic location:
Preferred name:
NM_014319.5(LEMD3):c.2023+1G>A
HGVS:
  • NC_000012.12:g.65240031G>A
  • NG_016210.2:g.75461G>A
  • NM_001167614.2:c.2020+1G>A
  • NM_014319.5:c.2023+1G>AMANE SELECT
  • NC_000012.11:g.65633811G>A
Links:
dbSNP: rs2136354712
NCBI 1000 Genomes Browser:
rs2136354712
Molecular consequence:
  • NM_001167614.2:c.2020+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_014319.5:c.2023+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
SCV002257809Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 14, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
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

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.

Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PC, Costa T, Janssens K, Menten B, Van Roy N, Vermeulen SJ, Savarirayan R, Van Hul W, Vanhoenacker F, Huylebroeck D, De Paepe A, Naeyaert JM, Vandesompele J, Speleman F, Verschueren K, Coucke PJ, Mortier GR.

Nat Genet. 2004 Nov;36(11):1213-8. Epub 2004 Oct 17.

PubMed [citation]
PMID:
15489854
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002257809.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

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. This variant has not been reported in the literature in individuals affected with LEMD3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 7 of the LEMD3 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 LEMD3 are known to be pathogenic (PMID: 15489854, 19438932).

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

Last Updated: Feb 20, 2024