ClinVar Genomic variation as it relates to human health
NM_001101426.4(CRPPA):c.1105GTT[3] (p.Val372del)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001101426.4(CRPPA):c.1105GTT[3] (p.Val372del)
Variation ID: 156455 Accession: VCV000156455.33
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 7p21.2 7: 16258393-16258395 (GRCh38) [ NCBI UCSC ] 7: 16298018-16298020 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 2, 2018 Apr 15, 2024 Sep 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001101426.4:c.1105GTT[3] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001094896.1:p.Val372del inframe deletion NM_001101426.4:c.1114_1116del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001101417.4:c.955GTT[3] NP_001094887.1:p.Val322del inframe deletion NM_001101426.3:c.1114_1116del NM_001101426.3:c.1114_1116delGTT NM_001368197.1:c.1000GTT[3] NP_001355126.1:p.Val337del inframe deletion NR_160656.1:n.1170GTT[3] non-coding transcript variant NC_000007.14:g.16258394ACA[3] NC_000007.13:g.16298019ACA[3] NG_032690.2:g.167919GTT[3] - Protein change
- V372del, V322del, V337del
- Other names
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- Canonical SPDI
- NC_000007.14:16258392:AACAACAACAACA:AACAACAACA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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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. |
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CRPPA | - | - |
GRCh38 GRCh37 |
508 | 756 | |
CRPPA-AS1 | - | - | - | GRCh38 | - | 140 |
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. |
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Likely pathogenic (2) |
criteria provided, single submitter
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Aug 7, 2018 | RCV000144516.10 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Sep 7, 2023 | RCV000596292.23 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 7, 2018 | RCV000714703.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 22, 2022 | RCV002228673.5 |
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. |
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Likely pathogenic
(Aug 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8
Affected status: yes
Allele origin:
inherited
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000845425.1
First in ClinVar: Nov 03, 2018 Last updated: Nov 03, 2018 |
Number of individuals with the variant: 1
Sex: male
Geographic origin: Iran
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Likely pathogenic
(Aug 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 7
Affected status: yes
Allele origin:
inherited
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000845426.1
First in ClinVar: Nov 03, 2018 Last updated: Nov 03, 2018 |
Number of individuals with the variant: 1
Sex: male
Geographic origin: Iran
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Pathogenic
(Oct 27, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000700976.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Sep 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004036976.1
First in ClinVar: Sep 30, 2023 Last updated: Sep 30, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Also known as ISPD c.1114_1116del p.(Val372del); This variant is associated with the following publications: (PMID: 23288328, 34485198, 27234031, 23390185, 31127727, 30708323, 31375477, 37526466, 34307571) (less)
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Likely pathogenic
(Apr 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003830180.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
Autosomal recessive limb-girdle muscular dystrophy type 2U
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
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Invitae
Accession: SCV002508424.3
First in ClinVar: May 16, 2022 Last updated: Feb 28, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 156455). This variant has been observed in individual(s) with ISPD-related conditions (PMID: 23288328, 23390185, 27234031, 31127727). … (more)
ClinVar contains an entry for this variant (Variation ID: 156455). This variant has been observed in individual(s) with ISPD-related conditions (PMID: 23288328, 23390185, 27234031, 31127727). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.1114_1116del, results in the deletion of 1 amino acid(s) of the ISPD protein (p.Val372del), but otherwise preserves the integrity of the reading frame. For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. (less)
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Pathogenic
(Apr 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249111.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Mar 05, 2013)
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no assertion criteria provided
Method: literature only
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MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 7
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000189835.4
First in ClinVar: Oct 14, 2014 Last updated: Sep 28, 2018 |
Comment on evidence:
In 2 sibs, born of consanguineous Italian parents, with limb-girdle muscular dystrophy-dystroglycanopathy type C7 (MDDGC7; 616052), Tasca et al. (2013) identified a homozygous 3-bp deletion … (more)
In 2 sibs, born of consanguineous Italian parents, with limb-girdle muscular dystrophy-dystroglycanopathy type C7 (MDDGC7; 616052), Tasca et al. (2013) identified a homozygous 3-bp deletion (c.1114_1116delGTT) in the ISPD gene, resulting in the deletion of a residue (Val372del) in the functional synthase domain. The mutation was not found in 400 Italian control chromosomes or in the Exome Variant Server database. The patients had childhood-onset proximal muscle weakness affecting the upper and lower extremities; muscle biopsy showed dystrophic changes and hypoglycosylation of alpha-dystroglycan. There were no cognitive or ocular abnormalities. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service. | Westra D | Journal of neuromuscular diseases | 2019 | PMID: 31127727 |
Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population. | Fattahi Z | Clinical genetics | 2017 | PMID: 27234031 |
Limb-girdle muscular dystrophy with α-dystroglycan deficiency and mutations in the ISPD gene. | Tasca G | Neurology | 2013 | PMID: 23390185 |
ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies. | Cirak S | Brain : a journal of neurology | 2013 | PMID: 23288328 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ISPD | - | - | - | - |
Text-mined citations for rs587777798 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.