NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 22, 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:: RCV001228238.6

Allele description [Variation Report for NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs)]

NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs)

Gene:

POMT2:protein O-mannosyltransferase 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs)

HGVS:

NC_000014.9:g.77291374_77291375dup
NG_008897.1:g.34509_34510dup
NM_013382.7:c.1123_1124dupMANE SELECT
NP_037514.2:p.Tyr376fs
NP_037514.2:p.Tyr376fs
LRG_844t1:c.1123_1124dup
LRG_844:g.34509_34510dup
LRG_844p1:p.Tyr376fs
NC_000014.8:g.77757715_77757716insGT
NC_000014.8:g.77757717_77757718dup
NM_013382.5:c.1123_1124dup

Protein change:

Y376fs

Links:

dbSNP: rs886042401

NCBI 1000 Genomes Browser:

rs886042401

Molecular consequence:

NM_013382.7:c.1123_1124dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 2; WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, POMT2-RELATED; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A2
Identifiers:: MONDO: MONDO:0013154; MedGen: C3150411; Orphanet: 588; Orphanet: 899; OMIM: 613150

Name:: Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (MDDGB2)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, POMT2-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 2
Identifiers:: MONDO: MONDO:0013160; MedGen: C3150416; OMIM: 613156

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2N
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMT2-RELATED; Limb-girdle muscular dystrophy-dystroglycanopathy, type C2; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2
Identifiers:: MONDO: MONDO:0013162; MedGen: C3150418; Orphanet: 206559; OMIM: 613158

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001400628	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15894594, 22323514, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001400628

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 22, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome.

van Reeuwijk J, Janssen M, van den Elzen C, Beltran-Valero de Bernabé D, Sabatelli P, Merlini L, Boon M, Scheffer H, Brockington M, Muntoni F, Huynen MA, Verrips A, Walsh CA, Barth PG, Brunner HG, van Bokhoven H.

J Med Genet. 2005 Dec;42(12):907-12. Epub 2005 May 13.

PubMed [citation]

PMID:: 15894594
PMCID:: PMC1735967

Cobblestone lissencephaly: neuropathological subtypes and correlations with genes of dystroglycanopathies.

Devisme L, Bouchet C, Gonzalès M, Alanio E, Bazin A, Bessières B, Bigi N, Blanchet P, Bonneau D, Bonnières M, Bucourt M, Carles D, Clarisse B, Delahaye S, Fallet-Bianco C, Figarella-Branger D, Gaillard D, Gasser B, Delezoide AL, Guimiot F, Joubert M, Laurent N, et al.

Brain. 2012 Feb;135(Pt 2):469-82. doi: 10.1093/brain/awr357. Epub 2012 Feb 9.

PubMed [citation]

PMID:: 22323514

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001400628.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Tyr376Profs*23) in the POMT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT2 are known to be pathogenic (PMID: 15894594). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of muscular dystrophy-dystroglycanopathy (PMID: 22323514). This variant is also known as c.1124insAC. ClinVar contains an entry for this variant (Variation ID: 282447). 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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