NM_152490.5(B3GALNT2):c.979G>A (p.Asp327Asn) AND Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 28, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001854841.7

Allele description [Variation Report for NM_152490.5(B3GALNT2):c.979G>A (p.Asp327Asn)]

NM_152490.5(B3GALNT2):c.979G>A (p.Asp327Asn)

Gene:

B3GALNT2:beta-1,3-N-acetylgalactosaminyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.3

Genomic location:

Preferred name:

NM_152490.5(B3GALNT2):c.979G>A (p.Asp327Asn)

HGVS:

NC_000001.11:g.235458649C>T
NG_033219.2:g.50833G>A
NM_152490.5:c.979G>AMANE SELECT
NP_689703.1:p.Asp327Asn
NC_000001.10:g.235621957C>T
NM_152490.2:c.979G>A

Protein change:

D327N

Links:

dbSNP: rs753340395

NCBI 1000 Genomes Browser:

rs753340395

Molecular consequence:

NM_152490.5:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (MDDGA11)
Synonyms:: WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, B3GALNT2-RELATED; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A11; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11
Identifiers:: MONDO: MONDO:0014071; MedGen: C3554638; Orphanet: 588; Orphanet: 899; OMIM: 615181

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002248425	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24084573, 25326637, 29273094, 33290285, 28492532
SCV003829700	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 3, 2021)	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

SCV002248425

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 28, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003829700

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 3, 2021)

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

B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations.

Hedberg C, Oldfors A, Darin N.

Eur J Hum Genet. 2014 May;22(5):707-10. doi: 10.1038/ejhg.2013.223. Epub 2013 Oct 2.

PubMed [citation]

PMID:: 24084573
PMCID:: PMC3992579

Clinical exome sequencing for genetic identification of rare Mendelian disorders.

Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF.

JAMA. 2014 Nov 12;312(18):1880-7. doi: 10.1001/jama.2014.14604.

PubMed [citation]

PMID:: 25326637
PMCID:: PMC4278636

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002248425.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 327 of the B3GALNT2 protein (p.Asp327Asn). This variant is present in population databases (rs753340395, gnomAD 0.004%). This missense change has been observed in individual(s) with B3GALNT2-related conditions (PMID: 24084573, 25326637, 29273094, 33290285). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 242531). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on B3GALNT2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

From Revvity Omics, Revvity, SCV003829700.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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