NM_001281463.1(SMC1A):c.345+6C>T AND Congenital muscular hypertrophy-cerebral syndrome

Clinical significance:Uncertain significance (Last evaluated: Mar 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001303311.1

Allele description [Variation Report for NM_001281463.1(SMC1A):c.345+6C>T]

NM_001281463.1(SMC1A):c.345+6C>T

Gene:
SMC1A:structural maintenance of chromosomes 1A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.22
Genomic location:
Preferred name:
NM_001281463.1(SMC1A):c.345+6C>T
HGVS:
  • NC_000023.11:g.53414752G>A
  • NG_006988.2:g.12919C>T
  • NM_001281463.1:c.345+6C>T
  • NM_006306.3:c.411+6C>T
  • LRG_773t1:c.345+6C>T
  • LRG_773t2:c.411+6C>T
  • LRG_773:g.12919C>T
  • NC_000023.10:g.53441701G>A
Links:
dbSNP: rs782515915
NCBI 1000 Genomes Browser:
rs782515915
Molecular consequence:
  • NM_001281463.1:c.345+6C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_006306.3:c.411+6C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Congenital muscular hypertrophy-cerebral syndrome (CDLS2)
Synonyms:
Cornelia de Lange syndrome 2
Identifiers:
MONDO: MONDO:0010370; MedGen: C1802395; Orphanet: 199; OMIM: 300590

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001492552Invitaecriteria provided, single submitter
Uncertain significance
(Mar 28, 2020)
germlineclinical testing

PubMed (3)
[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

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

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001492552.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change falls in intron 3 of the SMC1A gene. It does not directly change the encoded amino acid sequence of the SMC1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs782515915, ExAC 0.002%). This variant has not been reported in the literature in individuals with SMC1A-related disease. ClinVar contains an entry for this variant (Variation ID: 493525). Nucleotide substitutions within 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 is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.

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

Last Updated: Oct 7, 2021

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