ClinVar Genomic variation as it relates to human health
NM_002979.5(SCP2):c.572A>G (p.His191Arg)
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
-
NM_002979.5(SCP2):c.572A>G (p.His191Arg)
Variation ID: 1050589 Accession: VCV001050589.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p32.3 1: 52974817 (GRCh38) [ NCBI UCSC ] 1: 53440489 (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 Apr 13, 2021 Feb 7, 2023 Jul 30, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_002979.5:c.572A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002970.2:p.His191Arg missense NM_001007098.3:c.440A>G NP_001007099.1:p.His147Arg missense NM_001193599.2:c.500A>G NP_001180528.1:p.His167Arg missense NM_001193600.2:c.440A>G NP_001180529.1:p.His147Arg missense NM_001193617.2:c.329A>G NP_001180546.1:p.His110Arg missense NM_001330587.2:c.572A>G NP_001317516.1:p.His191Arg missense NC_000001.11:g.52974817A>G NC_000001.10:g.53440489A>G NG_012211.1:g.52542A>G - Protein change
- H110R, H147R, H167R, H191R
- Other names
- -
- Canonical SPDI
- NC_000001.11:52974816:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00004
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
- Links
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 | ||
---|---|---|---|---|---|---|
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. |
|||
SCP2 | - | - |
GRCh38 GRCh37 |
422 | 443 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
no assertion criteria provided
|
- | RCV001358209.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jul 30, 2022 | RCV001871949.4 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Jul 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002269496.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 191 of the SCP2 protein (p.His191Arg). … (more)
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 191 of the SCP2 protein (p.His191Arg). This variant is present in population databases (rs372168791, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SCP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1050589). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
Sterol carrier protein 2 deficiency
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553882.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
SCP2, c.572A>G, p.His191Arg, Heterozygous, Uncertain SignificanceVariant Interpretation: The p.His191Arg was not identified in the literature, nor was it identified in ClinVar or LOVD 3.0 databases. … (more)
SCP2, c.572A>G, p.His191Arg, Heterozygous, Uncertain SignificanceVariant Interpretation: The p.His191Arg was not identified in the literature, nor was it identified in ClinVar or LOVD 3.0 databases. The variant was identified in dbSNP (rs372168791). The variant was identified in control databases in 11 of 282548 chromosomes at a frequency of 0.00003893 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Other in 2 of 7204 chromosomes (freq: 0.000278), European (non-Finnish) in 9 of 129022 chromosomes (freq: 0.00007), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.His191 residue is conserved in mammals and other organisms, and 8 of 8 computational analyses (SIFT, FAHTMM, DANN, MT, MetaLR, Revel, PolyPhen, MutationTaster) suggest that the variant may impact the protein: however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.Disease Information: Homozygous pathogenic variants in SCP2 have been reported in a patient with leukoencephalopathy with dystonia and motor neuropathy (OMIM: 613724, Ferdinandusse_2006_PMID: 16685654). The patient was a 45-year old man with a 28-year history of dystonic head tremor and spasmodic torticollis, as well as spasmodic torticollis (onset 17 years) with dystonic head tremor in stressful situations. Fertility checkup at age 29 revealed hypergonadotrophic hypogonadism and azoospermia. Cranial magnetic resonance imaging (MRI) showed bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region. Neurologic examination revealed hyposmia, pathologic saccadic eye movements, and a slight hypoacusis. Deep tendon reflexes were brisk in the arms but diminished in the lower extremities. There were slight cerebellar signs, with left-sided intention tremor and rebound phenomenon. Metabolite analyses of plasma revealed an accumulation of branched-chain pristanic acid, and abnormal bile alcohol glucuronides were excreted in urine. In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by Western blotting. (Verbatim, OMIM:613724) Compound heterozygous truncating variants in SCP2 have also been identified in a 51-year-old man with hand clumsiness in his 30s, followed by gait disturbance, deafness, slow ocular saccades, impaired priorioceptoin, mild dysmetria and dysdiadochokinesis. (Horvath_2015_PMID: 26497993). Biochemical analyses showed increased alanine transaminase (88 U/L, normal <40), gamma glutamyl transferase (78 U/L, normal <70), α-fetoprotein (63 kU/L, normal <10), creatine kinase (777 U/L, normal <40–320), and ferritin (539 μg/L, normal <300 in men). Copper and ceruloplasmin were normal, as was the blood count, vitamin B12, and folate. Free carnitine (65 μmol/L, normal <52) and total carnitine (85.6 μmol/L, normal <63) were increased, and there was a nonspecific increase in long chain hydroxylacylcarnitines. (Horvath_2015_PMID: 26497993).Familial Risk: Leukoencephalopathy with dystonia and motor neuropathy is inherited in an autosomal recessive manner. At conception, the siblings of an affected individual have a 25% chance of being affected, a 50% chance of being asymptomatic carriers, and a 25% chance of being unaffected and not carriers. Carrier testing for at-risk relatives at increased risk is possible if the pathogenic variants in the family are known. (less)
|
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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs372168791 ...
HelpRecord last updated Dec 25, 2023
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.