VCV000691982.15 - ClinVar

NM_001077365.2(POMT1):c.280+1G>T

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(7)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001077365.2(POMT1):c.280+1G>T

Variation ID: 691982 Accession: VCV000691982.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.13 9: 131506454 (GRCh38) [ NCBI UCSC ] 9: 134381841 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 20, 2019	Jun 17, 2024	Mar 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001077365.2:c.280+1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001077366.2:c.118+1G>T		splice donor
NM_001136113.2:c.280+1G>T		splice donor
NM_001136114.2:c.-72+1G>T		splice donor
NM_001353193.2:c.280+1G>T		splice donor
NM_001353194.2:c.118+1G>T		splice donor
NM_001353195.2:c.-72+1G>T		splice donor
NM_001353196.2:c.173+1G>T		splice donor
NM_001353197.2:c.118+1G>T		splice donor
NM_001353198.2:c.118+1G>T		splice donor
NM_001353199.2:c.-72+1G>T		splice donor
NM_001353200.2:c.-30+1G>T		splice donor
NM_001374689.1:c.118+1G>T		splice donor
NM_001374690.1:c.280+1G>T		splice donor
NM_001374691.1:c.-71-914G>T		intron variant
NM_001374692.1:c.-71-914G>T		intron variant
NM_001374693.1:c.118+1G>T		splice donor
NM_001374695.1:c.-30+2114G>T		intron variant
NM_001411024.1:c.-710+1G>T		splice donor
NM_007171.4:c.280+1G>T		splice donor
NC_000009.12:g.131506454G>T
NC_000009.11:g.134381841G>T
NG_008896.2:g.8553G>T
LRG_842:g.8553G>T
LRG_842t1:c.280+1G>T
LRG_842t2:c.280+1G>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000009.12:131506453:G:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Links

dbSNP: rs746823238 ClinGen: CA5293206 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
POMT1		-	-	GRCh38 GRCh37	1173	1214

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Mar 25, 2024	RCV000853233.9
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 15, 2021	RCV001683668.2
Autosomal recessive limb-girdle muscular dystrophy type 2K Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Walker-Warburg congenital muscular dystrophy	Pathogenic (1)	criteria provided, single submitter	Jan 9, 2024	RCV001869305.6

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Affected status: yes Allele origin: germline	Pathology and Clinical Laboratory Medicine, King Fahad Medical City Accession: SCV000996296.1 First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019	Number of individuals with the variant: 3 Ethnicity/Population group: Arab Geographic origin: Middle East
Pathogenic (Jan 27, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001369949.2 First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020	Comment: This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3.
Pathogenic (Sep 15, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV001905652.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021	Clinical Features: Hydrocephalus (present) , Retinal atrophy (present) , Dandy-Walker malformation (present) , Cerebellar malformation (present) , Congenital muscular dystrophy (present) Sex: male
Pathogenic (Jan 09, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Walker-Warburg congenital muscular dystrophy Autosomal recessive limb-girdle muscular dystrophy type 2K Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002136342.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024	Publications: PubMed (2) PubMed: 18752264‚ 20065251 Comment: This sequence change affects a donor splice site in intron 4 of the POMT1 gene. RNA analysis indicates that disruption of this splice site induces … (more) This sequence change affects a donor splice site in intron 4 of the POMT1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs746823238, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with Walker-Warburg syndrome (PMID: 18752264, 20065251). This variant is also known as p.del77-93. ClinVar contains an entry for this variant (Variation ID: 691982). Studies have shown that disruption of this splice site results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 20065251). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 25, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004806002.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024
Pathogenic (Aug 28, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (Autosomal recessive inheritance) Affected status: yes Allele origin: biparental	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne Accession: SCV004847199.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Method: Exome sequencing
Pathogenic (Feb 28, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV001521029.2 First in ClinVar: Mar 22, 2021 Last updated: Jun 17, 2024

Comment:

This sequence change affects a donor splice site in intron 4 of the POMT1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs746823238, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with Walker-Warburg syndrome (PMID: 18752264, 20065251). This variant is also known as p.del77-93. ClinVar contains an entry for this variant (Variation ID: 691982). Studies have shown that disruption of this splice site results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 20065251). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies.	Lommel M	Neurology	2010	PMID: 20065251
Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East.	Manzini MC	Human mutation	2008	PMID: 18752264

Text-mined citations for rs746823238 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 19, 2025

ClinVar Genomic variation as it relates to human health

NM_001077365.2(POMT1):c.280+1G>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs746823238 ...