NM_017951.5(SMPD4):c.253G>T (p.Glu85Ter) AND Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 14, 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:: RCV001089883.1

Allele description [Variation Report for NM_017951.5(SMPD4):c.253G>T (p.Glu85Ter)]

NM_017951.5(SMPD4):c.253G>T (p.Glu85Ter)

Gene:

SMPD4:sphingomyelin phosphodiesterase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q21.1

Genomic location:

Preferred name:

NM_017951.5(SMPD4):c.253G>T (p.Glu85Ter)

HGVS:

NC_000002.12:g.130173530C>A
NG_053070.1:g.14221G>T
NM_001171083.2:c.244-635G>T
NM_017751.4:c.370G>T
NM_017951.5:c.253G>TMANE SELECT
NP_060221.2:p.Glu124Ter
NP_060421.2:p.Glu124Ter
NP_060421.3:p.Glu85Ter
NC_000002.11:g.130931103C>A
NM_017951.4:c.370G>T
NR_033232.3:n.371G>T

Protein change:

E124*

Links:

dbSNP: rs1688675737

NCBI 1000 Genomes Browser:

rs1688675737

Molecular consequence:

NM_001171083.2:c.244-635G>T - intron variant - [Sequence Ontology: SO:0001627]
NR_033232.3:n.371G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_017751.4:c.370G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017951.5:c.253G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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MULTISPECIES: FAD-dependent oxidoreductase [unclassified Paenibacillus]
MULTISPECIES: FAD-dependent oxidoreductase [unclassified Paenibacillus]
gi|950265692|ref|WP_057301882.1|

Protein
exopolysaccharide Pel transporter PelG [Paenibacillus sp. Root444D2]
exopolysaccharide Pel transporter PelG [Paenibacillus sp. Root444D2]
gi|950266584|ref|WP_057302772.1|

Protein
MULTISPECIES: TIR domain-containing protein [unclassified Paenibacillus]
MULTISPECIES: TIR domain-containing protein [unclassified Paenibacillus]
gi|950266954|ref|WP_057303141.1|

Protein
sugar-binding domain-containing protein [Paenibacillus sp. Root444D2]
sugar-binding domain-containing protein [Paenibacillus sp. Root444D2]
gi|950270395|ref|WP_057306576.1|

Protein
MULTISPECIES: transglycosylase domain-containing protein [unclassified Paenibaci...
MULTISPECIES: transglycosylase domain-containing protein [unclassified Paenibacillus]
gi|950266748|ref|WP_057302935.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001245384	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 14, 2020)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 31495489, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001245384

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 14, 2020)

unknown

curation

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV001245384.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

This variant is interpreted as likely pathogenic for Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PP1, PVS1-Srong.

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

Last Updated: Sep 16, 2024

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