NM_001077365.2(POMT1):c.699+67G>A AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 20, 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:: RCV001379440.1

Allele description

NM_001077365.2(POMT1):c.699+67G>A

Gene:

POMT1:protein O-mannosyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_001077365.2(POMT1):c.699+67G>A

HGVS:

NC_000009.12:g.131510063G>A
NG_008896.1:g.12162G>A
NG_008896.2:g.12162G>A
NM_001077365.2:c.699+67G>AMANE SELECT
NM_001077366.2:c.537+67G>A
NM_001136113.2:c.699+67G>A
NM_001136114.2:c.348+67G>A
NM_001353193.2:c.765+1G>A
NM_001353194.2:c.537+67G>A
NM_001353195.2:c.348+67G>A
NM_001353196.2:c.609+67G>A
NM_001353197.2:c.603+1G>A
NM_001353198.2:c.603+1G>A
NM_001353199.2:c.414+1G>A
NM_001353200.2:c.243+67G>A
NM_001374689.1:c.604G>A
NM_001374690.1:c.699+67G>A
NM_001374691.1:c.348+67G>A
NM_001374692.1:c.348+67G>A
NM_001374693.1:c.537+67G>A
NM_001374695.1:c.309+1G>A
NM_007171.4:c.765+1G>A
NP_001361618.1:p.Val202Ile
LRG_842t1:c.765+1G>A
LRG_842t2:c.699+67G>A
LRG_842:g.12162G>A
NC_000009.11:g.134385450G>A

Protein change:

V202I

Links:

dbSNP: rs776061161

NCBI 1000 Genomes Browser:

rs776061161

Molecular consequence:

NM_001077365.2:c.699+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001077366.2:c.537+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001136113.2:c.699+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001136114.2:c.348+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001353194.2:c.537+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001353195.2:c.348+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001353196.2:c.609+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001353200.2:c.243+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374690.1:c.699+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374691.1:c.348+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374692.1:c.348+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374693.1:c.537+67G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374689.1:c.604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353193.2:c.765+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353197.2:c.603+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353198.2:c.603+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001353199.2:c.414+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001374695.1:c.309+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007171.4:c.765+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2K
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1; MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2K; Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012248; MedGen: C1836373; Orphanet: 86812; OMIM: 609308

Name:: Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (MDDGB1)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, POMT1-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL IMPAIRMENT), TYPE B, 1
Identifiers:: MONDO: MONDO:0013159; MedGen: C3150415; OMIM: 613155

Name:: Walker-Warburg congenital muscular dystrophy (MDDGA1)
Synonyms:: HARD syndrome; Muscular dystrophy-dystroglycanopathy, type A; Walker-Warburg syndrome
Identifiers:: MONDO: MONDO:0000171; MedGen: C0265221; Orphanet: 899; OMIM: PS236670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001577243	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 20, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 12369018, 15637732, 16575835, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001577243

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 20, 2020)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome.

Beltrán-Valero de Bernabé D, Currier S, Steinbrecher A, Celli J, van Beusekom E, van der Zwaag B, Kayserili H, Merlini L, Chitayat D, Dobyns WB, Cormand B, Lehesjoki AE, Cruces J, Voit T, Walsh CA, van Bokhoven H, Brunner HG.

Am J Hum Genet. 2002 Nov;71(5):1033-43. Epub 2002 Oct 4.

PubMed [citation]

PMID:: 12369018
PMCID:: PMC419999

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001577243.1

#	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 affects a donor splice site in intron 8 of the POMT1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs776061161, ExAC 0.003%). This variant has not been reported in the literature in individuals with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 593922). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). 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

Last Updated: Apr 23, 2022

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