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NM_017951.5(SMPD4):c.1356_1362del (p.Leu453fs) AND Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 16, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000853218.1

Allele description [Variation Report for NM_017951.5(SMPD4):c.1356_1362del (p.Leu453fs)]

NM_017951.5(SMPD4):c.1356_1362del (p.Leu453fs)

Gene:
SMPD4:sphingomyelin phosphodiesterase 4 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q21.1
Genomic location:
Preferred name:
NM_017951.5(SMPD4):c.1356_1362del (p.Leu453fs)
HGVS:
  • NC_000002.12:g.130155190_130155196del
  • NG_053070.1:g.32558_32564del
  • NM_001171083.2:c.1167_1173del
  • NM_017751.4:c.1386_1392del
  • NM_017951.5:c.1356_1362delMANE SELECT
  • NP_001164554.1:p.Leu390fs
  • NP_060221.2:p.Leu463fs
  • NP_060421.2:p.Leu492fs
  • NP_060421.3:p.Leu453fs
  • NC_000002.11:g.130912763_130912769del
  • NM_017951.4:c.1473_1479del
  • NR_033231.3:n.1331_1337del
  • NR_033232.3:n.1311_1317del
Protein change:
L390fs
Links:
OMIM: 610457.0006; dbSNP: rs1573664291
NCBI 1000 Genomes Browser:
rs1573664291
Molecular consequence:
  • NM_001171083.2:c.1167_1173del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_017751.4:c.1386_1392del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_017951.5:c.1356_1362del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_033231.3:n.1331_1337del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_033232.3:n.1311_1317del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
Identifiers:
MONDO: MONDO:0032838; MedGen: C5231431; OMIM: 618622

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000996030OMIM
no assertion criteria provided
Pathogenic
(Oct 16, 2019) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis.

Magini P, Smits DJ, Vandervore L, Schot R, Columbaro M, Kasteleijn E, van der Ent M, Palombo F, Lequin MH, Dremmen M, de Wit MCY, Severino M, Divizia MT, Striano P, Ordonez-Herrera N, Alhashem A, Al Fares A, Al Ghamdi M, Rolfs A, Bauer P, Demmers J, Verheijen FW, et al.

Am J Hum Genet. 2019 Oct 3;105(4):689-705. doi: 10.1016/j.ajhg.2019.08.006. Epub 2019 Sep 5.

PubMed [citation]
PMID:
31495489
PMCID:
PMC6817560

Details of each submission

From OMIM, SCV000996030.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 4 deceased sibs, born of consanguineous Arab parents (family 10) with neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA; 618622), Magini et al. (2019) identified a homozygous 7-bp deletion (c.1473_1479del, NM_017951.4) in exon 15 of the SMPD4 gene, resulting in a frameshift and premature termination (Leu492GlnfsTer27). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function.

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

Last Updated: Sep 16, 2024