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NM_000751.3(CHRND):c.1371+1G>T AND Lethal multiple pterygium syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 15, 2022
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:
RCV003121053.5

Allele description [Variation Report for NM_000751.3(CHRND):c.1371+1G>T]

NM_000751.3(CHRND):c.1371+1G>T

Gene:
CHRND:cholinergic receptor nicotinic delta subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.1
Genomic location:
Preferred name:
NM_000751.3(CHRND):c.1371+1G>T
HGVS:
  • NC_000002.12:g.232534343G>T
  • NG_008028.1:g.13132G>T
  • NM_000751.3:c.1371+1G>TMANE SELECT
  • NM_001256657.2:c.1326+1G>T
  • NM_001311195.2:c.789+1G>T
  • NM_001311196.2:c.1068+1G>T
  • NC_000002.11:g.233399053G>T
Molecular consequence:
  • NM_000751.3:c.1371+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001256657.2:c.1326+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001311195.2:c.789+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001311196.2:c.1068+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Lethal multiple pterygium syndrome (LMPS)
Identifiers:
MONDO: MONDO:0009668; MedGen: C1854678; Orphanet: 33108; OMIM: 253290

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003784980Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 15, 2022) 		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

Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders.

Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Körber F, Blankenburg M, Mundlos S, Heller R, Hoffmann K.

Am J Hum Genet. 2008 Feb;82(2):464-76. doi: 10.1016/j.ajhg.2007.11.006.

PubMed [citation]
PMID:
18252226
PMCID:
PMC2427255

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003784980.3

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

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the CHRND protein in which other variant(s) (p.Arg464*) have been observed in individuals with CHRND-related conditions (PMID: 18252226). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 CHRND-related conditions. This sequence change affects a donor splice site in intron 11 of the CHRND gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

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

Last Updated: Sep 29, 2024