NM_014975.3(MAST1):c.580GAG[1] (p.Glu195del) AND Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 27, 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:: RCV000735989.2

Allele description [Variation Report for NM_014975.3(MAST1):c.580GAG[1] (p.Glu195del)]

NM_014975.3(MAST1):c.580GAG[1] (p.Glu195del)

Genes:

LOC117125587:CRISPRi-FlowFISH-validated KLF1 and PRDX2 regulatory element [Gene]
MAST1:microtubule associated serine/threonine kinase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_014975.3(MAST1):c.580GAG[1] (p.Glu195del)

Other names:

p.E194del

HGVS:

NC_000019.10:g.12847863GAG[1]
NG_054729.1:g.18933GAG[1]
NG_068125.1:g.453GAG[1]
NM_014975.2:c.579_581delGGA
NM_014975.3:c.580GAG[1]MANE SELECT
NP_055790.1:p.Glu195del
NC_000019.9:g.12958677GAG[1]
NM_014975.2:c.579_581delGGA
NM_014975.2:c.583_585del
NM_014975.2:c.583_585delGAG

Protein change:

E195del

Links:

OMIM: 612256.0001; dbSNP: rs1568408280

NCBI 1000 Genomes Browser:

rs1568408280

Molecular consequence:

NM_014975.3:c.580GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations
Identifiers:: MONDO: MONDO:0032648; MedGen: C4748927; OMIM: 618273

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000864193	OMIM	no assertion criteria provided	Pathogenic (Jan 10, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV005043275	Watson Genetic Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 27, 2022)	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

SCV000864193

OMIM

no assertion criteria provided

Pathogenic
(Jan 10, 2019)

germline

literature only

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

SCV005043275

Watson Genetic Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 27, 2022)

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

Citations

PubMed

Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations.

Tripathy R, Leca I, van Dijk T, Weiss J, van Bon BW, Sergaki MC, Gstrein T, Breuss M, Tian G, Bahi-Buisson N, Paciorkowski AR, Pagnamenta AT, Wenninger-Weinzierl A, Martinez-Reza MF, Landler L, Lise S, Taylor JC, Terrone G, Vitiello G, Del Giudice E, Brunetti-Pierri N, D'Amico A, et al.

Neuron. 2018 Dec 19;100(6):1354-1368.e5. doi: 10.1016/j.neuron.2018.10.044. Epub 2018 Nov 15.

PubMed [citation]

PMID:: 30449657
PMCID:: PMC6436622

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, SCV000864193.1

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

Description

In a 9-year-old Italian boy (patient 1) with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM; 618273), Tripathy et al. (2018) identified a de novo heterozygous 3-bp deletion (c.580_582delGAG) in the MAST1 gene, resulting in an in-frame deletion of conserved residue glu194 (glu194del, E194del). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. Glu194 is located in a hydrophobic core of a 4-helix bundle in a domain of unknown function (DUF1908). In vitro functional studies showed that the variant did not perturb the interaction of MAST1 with microtubules.

#	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 Watson Genetic Lab, SCV005043275.1

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

#	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: Dec 7, 2024

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