NM_001136157.2(OTUD5):c.1465G>A (p.Gly489Ser) AND Multiple congenital anomalies-neurodevelopmental syndrome, X-linked

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 6, 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:: RCV001290732.3

Allele description [Variation Report for NM_001136157.2(OTUD5):c.1465G>A (p.Gly489Ser)]

NM_001136157.2(OTUD5):c.1465G>A (p.Gly489Ser)

Gene:

OTUD5:OTU deubiquitinase 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001136157.2(OTUD5):c.1465G>A (p.Gly489Ser)

HGVS:

NC_000023.11:g.48923851C>T
NG_016262.2:g.286G>A
NM_001136157.2:c.1465G>AMANE SELECT
NM_001136158.2:c.1465G>A
NM_001136159.2:c.814G>A
NM_017602.4:c.1480G>A
NP_001129629.1:p.Gly489Ser
NP_001129630.1:p.Gly489Ser
NP_001129631.1:p.Gly272Ser
NP_060072.1:p.Gly494Ser
NC_000023.10:g.48781128C>T
NG_016262.1:g.286G>A
p.Gly494Ser

Protein change:

G272S; GLY494SER

Links:

OMIM: 300713.0002; dbSNP: rs2063620799

NCBI 1000 Genomes Browser:

rs2063620799

Molecular consequence:

NM_001136157.2:c.1465G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001136158.2:c.1465G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001136159.2:c.814G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017602.4:c.1480G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on RNA splicing [Variation Ontology: 0362]

Observations:

Condition(s)

Name:: Multiple congenital anomalies-neurodevelopmental syndrome, X-linked
Synonyms:: LINKED SYNDROME
Identifiers:: MONDO: MONDO:0025351; MedGen: C5542341; OMIM: 301056

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001478869	OMIM	no assertion criteria provided	Pathogenic (Feb 9, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001736861	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 6, 2021)	de novo	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

SCV001478869

OMIM

no assertion criteria provided

Pathogenic
(Feb 9, 2021)

germline

literature only

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

SCV001736861

Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 6, 2021)

de novo

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
African American	de novo	yes	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation.

Beck DB, Basar MA, Asmar AJ, Thompson JJ, Oda H, Uehara DT, Saida K, Pajusalu S, Talvik I, D'Souza P, Bodurtha J, Mu W, Barañano KW, Miyake N, Wang R, Kempers M, Tamada T, Nishimura Y, Okada S, Kosho T, Dale R, Mitra A, et al.

Sci Adv. 2021 Jan 20;7(4). doi:pii: eabe2116. 10.1126/sciadv.abe2116. Print 2021 Jan.

PubMed [citation]

PMID:: 33523931
PMCID:: PMC7817106

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 OMIM, SCV001478869.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 brothers (P1 and P2, family 1) with X-linked multiple congenital anomalies-neurodevelopmental disorder (MCAND; 301056), Beck et al. (2021) identified a hemizygous c.1480G-A transition in the OTUD5 gene, predicted to result in a gly494-to-ser (G494S) substitution. However, the mutation occurred at a splice site junction and caused abnormal intron retention associated with a reduction in OTUD5 mRNA and protein levels. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database. Patient-derived induced pluripotent stem cells showed defects in neuroectoderm differentiation as measured by the expression of neural crest marker proteins. Knock-in of the G494S mutation into mice resulted in embryonic lethality. The findings were consistent with a loss of function. The patients had a severe phenotype resulting in death in infancy.

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

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV001736861.1

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

Description

This individual has been published in PMID: 33523931.

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

Last Updated: Feb 18, 2023

ClinVar

Relating variation to medicine