NM_005052.3(RAC3):c.276T>A (p.Asn92Lys) AND Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 13, 2022
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:: RCV003482465.1

Allele description [Variation Report for NM_005052.3(RAC3):c.276T>A (p.Asn92Lys)]

NM_005052.3(RAC3):c.276T>A (p.Asn92Lys)

Gene:

RAC3:Rac family small GTPase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_005052.3(RAC3):c.276T>A (p.Asn92Lys)

HGVS:

NC_000017.11:g.82032997T>A
NM_001316307.2:c.276T>A
NM_005052.3:c.276T>AMANE SELECT
NP_001303236.1:p.Asn92Lys
NP_005043.1:p.Asn92Lys
NC_000017.10:g.79990873T>A

Protein change:

N92K

Molecular consequence:

NM_001316307.2:c.276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005052.3:c.276T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (NEDBAF)
Identifiers:: MONDO: MONDO:0032820; MedGen: C5231416; OMIM: 618577

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004167590	Centre de Genetique Humaine, Institut de Pathologie et de Genetique	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 13, 2022)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 38214746

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004167590

Centre de Genetique Humaine, Institut de Pathologie et de Genetique

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 13, 2022)

de novo

clinical testing

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
Causasian	de novo	yes	1	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

An unusual presentation of de novo RAC3 variation in prenatal diagnosis.

Meunier C, Cassart M, Kostyla K, Simonis N, Monestier O, Tessier A.

Childs Nerv Syst. 2024 May;40(5):1597-1602. doi: 10.1007/s00381-024-06285-z. Epub 2024 Jan 12.

PubMed [citation]

PMID:: 38214746
PMCID:: PMC11026260

Details of each submission

From Centre de Genetique Humaine, Institut de Pathologie et de Genetique, SCV004167590.1

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

Description

Missense variant not found in GnomAD database, affecting a highly conserved amino acid (down to C. Elegans) in the "small GTPase domain". In silico tools classify the variant as pathogenic (SIFT, PolyPhen2, CADD score 20.5). The variant was not observed in the parents of the affected foetus (maternity & paternity were confirmed) suggesting de novo variant. The first clinical suspicion was raised at 22 weeks of gestation. Based on ultrasound + foetal MRI the foetus exhibited multiple CNS malformations (see dedicated section). Foetopathology described facial dysmorphism (see dedicated section).

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

Last Updated: Jan 26, 2024

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