VCV002685732.1 - ClinVar

GRCh37/hg19 1q23.1-23.3(chr1:158001058-162858285)x1

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 1q23.1-23.3(chr1:158001058-162858285)x1

Variation ID: 2685732 Accession: VCV002685732.1

Type and length

copy number loss, -

Location

Cytogenetic: 1q23.1-23.3 1: 158001058-162858285 (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	Jan 26, 2024	Jan 26, 2024	Oct 10, 2022

HGVS

Protein change

Other names

Canonical SPDI

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.
SDHC		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	861	903
ACKR1		-	-	GRCh38 GRCh37	24	35
ADAMTS4		-	-	GRCh38 GRCh37	48	90
AIM2		-	-	GRCh38 GRCh37	23	34
APCS		-	-	GRCh38 GRCh37	14	24
APOA2		-	-	GRCh38 GRCh37	29	48
ARHGAP30		-	-	GRCh38 GRCh37	65	83
ATF6		-	-	GRCh38 GRCh37	431	451
ATP1A2		-	-	GRCh38 GRCh37	1222	1334
ATP1A4		-	-	GRCh38 GRCh37	71	89

There are 99 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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.
not provided	Likely pathogenic (1)	criteria provided, single submitter	Oct 10, 2022	RCV003483944.1

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.
Likely pathogenic (Oct 10, 2022)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV004230364.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: The copy number loss of 1q23.1q23.3 involves numerous protein-coding genes. There is emerging evidence that loss of function variants of MPZ are associated with late-onset … (more) The copy number loss of 1q23.1q23.3 involves numerous protein-coding genes. There is emerging evidence that loss of function variants of MPZ are associated with late-onset demyelinating Charcot Marie Tooth disease, specifically CMT1B neuropathy (OMIM 118200, Chavada 2012, DiVincenzo 2014, Howard 2021, Khadilkar 2017, Volodarsky 2021). Haploinsufficiency of SDHC causes autosomal dominant hereditary paragangliomas-3 (OMIM 605373) and in rare cases gastrointestinal stromal tumors (OMIM 606764), There are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on gene content and current literature, this copy number variant (CNV) is classified as likely pathogenic. References Chavada et al., J Clin Neuromuscul Dis. 2012 Jun;13(4):206-8. PMID: 22622165 Chonat et al., Front Physiol. 2019 Jul 3;10:815. PMID: 31333484 DiVincenzo et al., Mol Genet Genomic Med. 2014 Nov;2(6):522-9. PMID: 25614874 Howard et al., J Peripher Nerv Syst. 2021 Jun;26(2):177-183. PMID: 33960567 Khadilkar et al., Ann Indian Acad Neurol. 2017 Oct-Dec;20(4):425-429. PMID: 29184351 Miller et al., Genet Med. 2021 Aug;23(8):1381-1390. PMID: 34012068 Rigler et al., Genet Med. 2015 May;17(5):348-57. PMID: 25232849 Song et al., Front Genet. 2021 Sep 23;12:696624. PMID: 34630509 Volodarsky et al., J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792 (less)

Comment:

The copy number loss of 1q23.1q23.3 involves numerous protein-coding genes. There is emerging evidence that loss of function variants of MPZ are associated with late-onset demyelinating Charcot Marie Tooth disease, specifically CMT1B neuropathy (OMIM 118200, Chavada 2012, DiVincenzo 2014, Howard 2021, Khadilkar 2017, Volodarsky 2021). Haploinsufficiency of SDHC causes autosomal dominant hereditary paragangliomas-3 (OMIM 605373) and in rare cases gastrointestinal stromal tumors (OMIM 606764), There are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on gene content and current literature, this copy number variant (CNV) is classified as likely pathogenic. References Chavada et al., J Clin Neuromuscul Dis. 2012 Jun;13(4):206-8. PMID: 22622165 Chonat et al., Front Physiol. 2019 Jul 3;10:815. PMID: 31333484 DiVincenzo et al., Mol Genet Genomic Med. 2014 Nov;2(6):522-9. PMID: 25614874 Howard et al., J Peripher Nerv Syst. 2021 Jun;26(2):177-183. PMID: 33960567 Khadilkar et al., Ann Indian Acad Neurol. 2017 Oct-Dec;20(4):425-429. PMID: 29184351 Miller et al., Genet Med. 2021 Aug;23(8):1381-1390. PMID: 34012068 Rigler et al., Genet Med. 2015 May;17(5):348-57. PMID: 25232849 Song et al., Front Genet. 2021 Sep 23;12:696624. PMID: 34630509 Volodarsky et al., J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792

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

There 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 this variant ...

Record last updated Feb 04, 2024

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 1q23.1-23.3(chr1:158001058-162858285)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...