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NM_014140.4(SMARCAL1):c.2141+1G>A AND Schimke immuno-osseous dysplasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 6, 2020
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:
RCV001035735.5

Allele description [Variation Report for NM_014140.4(SMARCAL1):c.2141+1G>A]

NM_014140.4(SMARCAL1):c.2141+1G>A

Gene:
SMARCAL1:SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_014140.4(SMARCAL1):c.2141+1G>A
HGVS:
  • NC_000002.12:g.216464668G>A
  • NG_009771.1:g.57255G>A
  • NM_001127207.2:c.2141+1G>A
  • NM_014140.4:c.2141+1G>AMANE SELECT
  • LRG_108t1:c.2141+1G>A
  • LRG_108:g.57255G>A
  • NC_000002.11:g.217329391G>A
  • NM_014140.3:c.2141+1G>A
Links:
dbSNP: rs1694789584
NCBI 1000 Genomes Browser:
rs1694789584
Molecular consequence:
  • NM_001127207.2:c.2141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_014140.4:c.2141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Schimke immuno-osseous dysplasia (SIOD)
Synonyms:
Spondyloepiphyseal dysplasia nephrotic syndrome; Schimke syndrome; Schimke immunoosseous dysplasia
Identifiers:
MONDO: MONDO:0009458; MedGen: C0877024; Orphanet: 1830; OMIM: 242900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001199070Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(May 6, 2020) 		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

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, et al.

Nat Genet. 2002 Feb;30(2):215-20. Epub 2002 Jan 22.

PubMed [citation]
PMID:
11799392
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001199070.5

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

Description

This sequence change affects a donor splice site in intron 13 of the SMARCAL1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SMARCAL1 are known to be pathogenic (PMID: 11799392, 20301550). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SMARCAL1-related conditions. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Feb 20, 2024