NM_017951.5(SMPD4):c.2242_2260del (p.Ser748fs) AND Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003986027.1

Allele description [Variation Report for NM_017951.5(SMPD4):c.2242_2260del (p.Ser748fs)]

NM_017951.5(SMPD4):c.2242_2260del (p.Ser748fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2q21.1

Genomic location:

Preferred name:

NM_017951.5(SMPD4):c.2242_2260del (p.Ser748fs)

HGVS:

NC_000002.12:g.130152782_130152800del
NG_053070.1:g.34954_34972del
NM_001171083.2:c.2053_2071del
NM_017751.4:c.2272_2290del
NM_017951.5:c.2242_2260delMANE SELECT
NP_001164554.1:p.Ser685fs
NP_060221.2:p.Ser758fs
NP_060421.3:p.Ser748fs
NC_000002.11:g.130910355_130910373del
NM_017951.4:c.2359_2377del
NR_033230.2:n.3505_3523del19
NR_033231.3:n.2217_2235del
NR_033232.3:n.2197_2215del

Protein change:

S685fs

Molecular consequence:

NM_001171083.2:c.2053_2071del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017751.4:c.2272_2290del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017951.5:c.2242_2260del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_033231.3:n.2217_2235del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_033232.3:n.2197_2215del - 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

Recent activity

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ead/Ea22-like family protein [Escherichia coli]
ead/Ea22-like family protein [Escherichia coli]
gi|2776372173|ref|WP_367745156.1|

Protein
alkaline phosphatase [Escherichia coli]
alkaline phosphatase [Escherichia coli]
gi|2776426753|ref|WP_367775631.1|

Protein
DUF6731 family protein [Escherichia coli]
DUF6731 family protein [Escherichia coli]
gi|2776433443|ref|WP_367776533.1|

Protein
LOC124900337 [Homo sapiens]
LOC124900337 [Homo sapiens]
Gene ID:124900337

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004801860	Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004801860

Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

paternal

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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 Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, SCV004801860.1

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

Description

A previously undescribed nucleotide variant creates a frameshift p.Ser787LeufsTer62 in the SMPD4 gene. The variant was observed in compound heterozygous state with another LoF variant in an individual affected with microlissencephaly and arthrogryposis. Homozygous and compound heterozygous variants are reported in patients with Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies, 618622. The variant is not present in population database (gnomAD no frequency). 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.

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

Last Updated: Sep 16, 2024

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