NM_014140.4(SMARCAL1):c.416T>A (p.Leu139Ter) AND Schimke immuno-osseous dysplasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 30, 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:: RCV001928145.4

Allele description [Variation Report for NM_014140.4(SMARCAL1):c.416T>A (p.Leu139Ter)]

NM_014140.4(SMARCAL1):c.416T>A (p.Leu139Ter)

Gene:

SMARCAL1:SNF2 related chromatin remodeling annealing helicase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_014140.4(SMARCAL1):c.416T>A (p.Leu139Ter)

HGVS:

NC_000002.12:g.216415120T>A
NG_009771.1:g.7707T>A
NM_001127207.2:c.416T>A
NM_014140.4:c.416T>AMANE SELECT
NP_001120679.1:p.Leu139Ter
NP_054859.2:p.Leu139Ter
LRG_108:g.7707T>A
NC_000002.11:g.217279843T>A

Protein change:

L139*

Links:

dbSNP: rs2106014776

NCBI 1000 Genomes Browser:

rs2106014776

Molecular consequence:

NM_001127207.2:c.416T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_014140.4:c.416T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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elongation factor-2, partial [Rhodothamniella floridula]
elongation factor-2, partial [Rhodothamniella floridula]
gi|429326050|gb|AFZ78375.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002182367	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11799392, 20301550, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002182367

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 30, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Schimke Immunoosseous Dysplasia.

Lippner E, Lücke T, Salgado C, Boerkoel C, Lewis DB.

2002 Oct 1 [updated 2023 Mar 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301550

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002182367.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu139*) in the SMARCAL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMARCAL1 are known to be pathogenic (PMID: 11799392, 20301550).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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