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NM_017739.4(POMGNT1):c.1212-3_1212-2del AND Muscular dystrophy-dystroglycanopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 24, 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:
RCV002526998.3

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1212-3_1212-2del]

NM_017739.4(POMGNT1):c.1212-3_1212-2del

Genes:
POMGNT1:protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [Gene - OMIM - HGNC]
TSPAN1:tetraspanin 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_017739.4(POMGNT1):c.1212-3_1212-2del
HGVS:
  • NC_000001.11:g.46192592_46192593del
  • NG_009205.3:g.32713_32714del
  • NM_001243766.2:c.1212-3_1212-2del
  • NM_001290129.2:c.1146-3_1146-2del
  • NM_001290130.2:c.783-3_783-2del
  • NM_017739.4:c.1212-3_1212-2delMANE SELECT
  • LRG_701t1:c.1212-3_1212-2del
  • LRG_701t2:c.1212-3_1212-2del
  • LRG_701:g.32713_32714del
  • NC_000001.10:g.46658264_46658265del
  • NG_009205.2:g.32713_32714del
  • NM_017739.4:c.1212-3_1212-2delCAMANE SELECT
Links:
dbSNP: rs1064797111
NCBI 1000 Genomes Browser:
rs1064797111
Molecular consequence:
  • NM_001243766.2:c.1212-3_1212-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001290129.2:c.1146-3_1146-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001290130.2:c.783-3_783-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_017739.4:c.1212-3_1212-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Muscular dystrophy-dystroglycanopathy
Synonyms:
Congenital muscular dystrophy due to dystroglycanopathy
Identifiers:
MONDO: MONDO:0018276; MedGen: C5679911; Orphanet: 370953

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003761173Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 24, 2023) 		germlinecuration

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761173.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The c.1212-3_1212-2del variant in POMGNT1 has been reported in one individual, in the compound heterozygous state, with muscular dystrophy-dystroglycanopathy (ClinVar accession number SCV002029242.2), and has been identified in 0.005% (1/18386) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1064797111). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#:424898) and has been interpreted as likely pathogenic by Invitae and CeGaT Center for Human Genetics Tuebingen and as a variant of uncertain significance by Royal Melbourne Hospital Molecular Genetics. This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 9 bases from the intron-exon boundary, providing evidence that this variant may delete 3 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_moderate, PM2_supporting, PM3 (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024