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NM_017777.4(MKS1):c.858+1G>A AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 22, 2023
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:
RCV003767996.2

Allele description [Variation Report for NM_017777.4(MKS1):c.858+1G>A]

NM_017777.4(MKS1):c.858+1G>A

Gene:
MKS1:MKS transition zone complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q22
Genomic location:
Preferred name:
NM_017777.4(MKS1):c.858+1G>A
HGVS:
  • NC_000017.11:g.58212981C>T
  • NG_013032.1:g.11625G>A
  • NM_001321268.2:c.249+1G>A
  • NM_001321269.2:c.858+1G>A
  • NM_001330397.2:c.858+1G>A
  • NM_001411113.1:c.858+1G>A
  • NM_017777.4:c.858+1G>AMANE SELECT
  • LRG_687t1:c.858+1G>A
  • LRG_687:g.11625G>A
  • NC_000017.10:g.56290342C>T
  • NM_017777.3:c.858+1G>A
Links:
dbSNP: rs756102768
NCBI 1000 Genomes Browser:
rs756102768
Molecular consequence:
  • NM_001321268.2:c.249+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001321269.2:c.858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001330397.2:c.858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001411113.1:c.858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_017777.4:c.858+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Familial aplasia of the vermis
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300
Name:
Meckel-Gruber syndrome
Synonyms:
DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:
MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004588224Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Oct 22, 2023)
germlineclinical testing

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

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

Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?

Tallila J, Salonen R, Kohlschmidt N, Peltonen L, Kestilä M.

Hum Mutat. 2009 Aug;30(8):E813-30. doi: 10.1002/humu.21057.

PubMed [citation]
PMID:
19466712
PMCID:
PMC2718326
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004588224.1

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

Description

This sequence change affects a donor splice site in intron 8 of the MKS1 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 MKS1 are known to be pathogenic (PMID: 19466712, 24886560, 26490104). This variant is present in population databases (rs756102768, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 556312). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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

Last Updated: Sep 29, 2024