VCV002951641.1 - ClinVar

NM_001077365.2(POMT1):c.1136_1137dup (p.Gln380fs)

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_001077365.2(POMT1):c.1136_1137dup (p.Gln380fs)

Variation ID: 2951641 Accession: VCV002951641.1

Type and length

Duplication, 2 bp

Location

Cytogenetic: 9q34.13 9: 131513290-131513291 (GRCh38) [ NCBI UCSC ] 9: 134388677-134388678 (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	Sep 5, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001077365.2:c.1136_1137dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001070833.1:p.Gln380fs	frameshift
NM_001077366.2:c.974_975dup	NP_001070834.1:p.Gln326fs	frameshift
NM_001136113.2:c.1136_1137dup	NP_001129585.1:p.Gln380fs	frameshift
NM_001136114.2:c.785_786dup	NP_001129586.1:p.Gln263fs	frameshift
NM_001353193.2:c.1202_1203dup	NP_001340122.2:p.Gln402fs	frameshift
NM_001353194.2:c.974_975dup	NP_001340123.1:p.Gln326fs	frameshift
NM_001353195.2:c.785_786dup	NP_001340124.1:p.Gln263fs	frameshift
NM_001353196.2:c.1046_1047dup	NP_001340125.1:p.Gln350fs	frameshift
NM_001353197.2:c.1040_1041dup	NP_001340126.2:p.Gln348fs	frameshift
NM_001353198.2:c.1040_1041dup	NP_001340127.2:p.Gln348fs	frameshift
NM_001353199.2:c.851_852dup	NP_001340128.2:p.Gln285fs	frameshift
NM_001353200.2:c.680_681dup	NP_001340129.1:p.Gln228fs	frameshift
NM_001374689.1:c.1124_1125dup	NP_001361618.1:p.Gln376fs	frameshift
NM_001374690.1:c.1136_1137dup	NP_001361619.1:p.Gln380fs	frameshift
NM_001374691.1:c.785_786dup	NP_001361620.1:p.Gln263fs	frameshift
NM_001374692.1:c.785_786dup	NP_001361621.1:p.Gln263fs	frameshift
NM_001374693.1:c.824+1825_824+1826dup		intron variant
NM_001374695.1:c.746_747dup	NP_001361624.1:p.Gln250fs	frameshift
NM_001411024.1:c.5_6dup	NP_001397953.1:p.Gln3fs	frameshift
NM_007171.4:c.1202_1203dup	NP_009102.4:p.Gln402fs	frameshift
NR_148391.2:n.1170_1171dup		non-coding transcript variant
NR_148392.2:n.1388_1389dup		non-coding transcript variant
NR_148393.2:n.1170_1171dup		non-coding transcript variant
NR_148394.2:n.1063_1064dup		non-coding transcript variant
NR_148395.2:n.1322_1323dup		non-coding transcript variant
NR_148396.2:n.956_957dup		non-coding transcript variant
NR_148397.2:n.1220_1221dup		non-coding transcript variant
NR_148398.2:n.1175_1176dup		non-coding transcript variant
NR_148399.2:n.1562_1563dup		non-coding transcript variant
NR_148400.2:n.1161_1162dup		non-coding transcript variant
NC_000009.12:g.131513292_131513293dup
NC_000009.11:g.134388679_134388680dup
NG_008896.2:g.15391_15392dup
NG_117886.1:g.574_575dup
NG_117887.1:g.73_74dup
LRG_842:g.15391_15392dup
LRG_842t1:c.1202_1203dup	LRG_842p1:p.Gln402fs
LRG_842t2:c.1136_1137dup	LRG_842p2:p.Gln380fs

... more HGVS ... less HGVS

Protein change

Q326fs, Q228fs, Q263fs, Q285fs, Q350fs, Q376fs, Q380fs, Q402fs, Q250fs, Q348fs, Q3fs

Other names

Canonical SPDI

NC_000009.12:131513290:GTG:GTGTG

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.
POMT1		-	-	GRCh38 GRCh37	1160	1201

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 2K Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Walker-Warburg congenital muscular dystrophy	Pathogenic (1)	criteria provided, single submitter	Sep 5, 2023	RCV003812328.2

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 (Sep 05, 2023)	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: SCV004607047.1 First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024	Publications: PubMed (3) PubMed: 12369018‚ 15637732‚ 16575835 Comment: For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POMT1-related conditions. … (more) For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POMT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln402Cysfs*7) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POMT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln402Cysfs*7) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835).

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
The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation.	van Reeuwijk J	Human mutation	2006	PMID: 16575835
Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome.	Currier SC	American journal of medical genetics. Part A	2005	PMID: 15637732
Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome.	Beltrán-Valero de Bernabé D	American journal of human genetics	2002	PMID: 12369018

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_001077365.2(POMT1):c.1136_1137dup (p.Gln380fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...