VCV002947427.1 - ClinVar

NM_017739.4(POMGNT1):c.1725_1726del (p.Val576fs)

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.

(1)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_017739.4(POMGNT1):c.1725_1726del (p.Val576fs)

Variation ID: 2947427 Accession: VCV002947427.1

Type and length

Deletion, 2 bp

Location

Cytogenetic: 1p34.1 1: 46189913-46189914 (GRCh38) [ NCBI UCSC ] 1: 46655585-46655586 (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	Feb 29, 2024	Feb 28, 2024	May 2, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_017739.4:c.1725_1726del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_060209.4:p.Val576fs	frameshift
NM_001243766.2:c.1725_1726del	NP_001230695.2:p.Val576fs	frameshift
NM_001290129.2:c.1659_1660del	NP_001277058.2:p.Val554fs	frameshift
NM_001290130.2:c.1296_1297del	NP_001277059.2:p.Val433fs	frameshift
NM_001410783.1:c.1725_1726del	NP_001397712.1:p.Val576fs	frameshift
NR_024332.1:n.2376_2377delCG
NC_000001.11:g.46189913_46189914del
NC_000001.10:g.46655585_46655586del
NG_009205.3:g.35392_35393del
LRG_701:g.35392_35393del
LRG_701t1:c.1725_1726del	LRG_701p1:p.Val576fs
LRG_701t2:c.1725_1726del	LRG_701p2:p.Val576fs

... more HGVS ... less HGVS

Protein change

V576fs, V433fs, V554fs

Other names

Canonical SPDI

NC_000001.11:46189912:CG:

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.

Links

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.
POMGNT1		-	-	GRCh38 GRCh37	262	1427
TSPAN1		-	-	GRCh38 GRCh37	15	1156

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.
Autosomal recessive limb-girdle muscular dystrophy type 2O Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3	Pathogenic (1)	criteria provided, single submitter	May 2, 2023	RCV003804057.2

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 (May 02, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2O Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 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: SCV004595027.1 First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024	Publications: PubMed (5) PubMed: 19299310‚ 20816175‚ 21447391‚ 26908613‚ 27391550 Comment: This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not … (more) This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This sequence change creates a premature translational stop signal (p.Val576Glyfs*9) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550). (less)

Comment:

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This sequence change creates a premature translational stop signal (p.Val576Glyfs*9) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550).

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
Homozygosity Mapping and Whole-Genome Sequencing Links a Missense Mutation in POMGNT1 to Autosomal Recessive Retinitis Pigmentosa.	Wang NH	Investigative ophthalmology & visual science	2016	PMID: 27391550
Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa.	Xu M	Human molecular genetics	2016	PMID: 26908613
Reactive gliosis of astrocytes and Müller glial cells in retina of POMGnT1-deficient mice.	Takahashi H	Molecular and cellular neurosciences	2011	PMID: 21447391
POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies.	Endo T	Methods in enzymology	2010	PMID: 20816175
Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.	Mercuri E	Neurology	2009	PMID: 19299310

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_017739.4(POMGNT1):c.1725_1726del (p.Val576fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...