NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter) AND Congenital disorder of glycosylation, type iit

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 18, 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:: RCV001095798.3

Allele description [Variation Report for NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter)]

NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter)

Gene:

GALNT2:polypeptide N-acetylgalactosaminyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.13

Genomic location:

Preferred name:

NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter)

Other names:

GALNT2, ARG200TER (rs1431963909)

HGVS:

NC_000001.11:g.230236716C>T
NG_011854.2:g.183928C>T
NM_001291866.2:c.484C>T
NM_004481.5:c.598C>TMANE SELECT
NP_001278795.1:p.Arg162Ter
NP_004472.1:p.Arg200Ter
NC_000001.10:g.230372462C>T
NM_004481.4:c.598C>T

Protein change:

R162*; ARG200TER

Links:

OMIM: 602274.0003; dbSNP: rs1431963909

NCBI 1000 Genomes Browser:

rs1431963909

Molecular consequence:

NM_001291866.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004481.5:c.598C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Congenital disorder of glycosylation, type iit
Synonyms:: CDG IIt
Identifiers:: MONDO: MONDO:0030043; MedGen: C5394387; OMIM: 618885

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001251641	OMIM	no assertion criteria provided	Pathogenic (May 21, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001468556	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 18, 2020)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 32293671, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001251641

OMIM

no assertion criteria provided

Pathogenic
(May 21, 2020)

germline

literature only

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

SCV001468556

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 18, 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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function.

Zilmer M, Edmondson AC, Khetarpal SA, Alesi V, Zaki MS, Rostasy K, Madsen CG, Lepri FR, Sinibaldi L, Cusmai R, Novelli A, Issa MY, Fenger CD, Abou Jamra R, Reutter H, Briuglia S, Agolini E, Hansen L, Petäjä-Repo UE, Hintze J, Raymond KM, Liedtke K, et al.

Brain. 2020 Apr 1;143(4):1114-1126. doi: 10.1093/brain/awaa063.

PubMed [citation]

PMID:: 32293671
PMCID:: PMC7534148

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, SCV001251641.1

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

Description

In a girl (patient C from family 2) with congenital disorder of glycosylation type IIt (CDG2T; 618885), who was born of Italian parents with possible remote consanguinity, Zilmer et al. (2020) identified a homozygous c.598C-T transition, resulting in an arg200-to-ter (R200X) substitution. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. The variant was found once in heterozygous state in the gnomAD database. Western blot analysis of patient plasma showed only nonglycosylated APOC3 (107720), consistent with a loss-of-function effect of the mutation.

#	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 SIB Swiss Institute of Bioinformatics, SCV001468556.1

#	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 Pathogenic for Congenital disorder of glycosylation 2T, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Predicted nullvariant in a gene where LOF is a known mechanism of disease (PVS1 downgraded to strong); Well-established functional studies show a deleterious effect (PS3).

#	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: Nov 25, 2023

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