NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter) AND Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 2023
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:: RCV000817910.3

Allele description [Variation Report for NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter)]

NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter)

Gene:

POMGNT2:protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.1

Genomic location:

Preferred name:

NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter)

HGVS:

NC_000003.12:g.43080390G>A
NG_032930.1:g.30694C>T
NM_032806.6:c.1042C>TMANE SELECT
NP_116195.2:p.Gln348Ter
LRG_706t1:c.1042C>T
LRG_706:g.30694C>T
LRG_706p1:p.Gln348Ter
NC_000003.11:g.43121882G>A
NM_032806.5:c.1042C>T

Protein change:

Q348*

Links:

dbSNP: rs1021357430

NCBI 1000 Genomes Browser:

rs1021357430

Molecular consequence:

NM_032806.6:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (MDDGA8)
Synonyms:: WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, GTDC2-RELATED
Identifiers:: MONDO: MONDO:0013904; MedGen: C3553813; Orphanet: 899; OMIM: 614830

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000958495	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	germline	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

SCV000958495

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000958495.3

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

Description

This sequence change creates a premature translational stop signal (p.Gln348*) in the POMGNT2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 233 amino acid(s) of the POMGNT2 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of Walker-Warburg syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 660661). This variant disrupts a region of the POMGNT2 protein in which other variant(s) (p.Glu519*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Mar 5, 2024

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