VCV000594101.9 - ClinVar

NM_012463.4(ATP6V0A2):c.118-7_118-3del

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.

(3)

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.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_012463.4(ATP6V0A2):c.118-7_118-3del

Variation ID: 594101 Accession: VCV000594101.9

Type and length

Deletion, 5 bp

Location

Cytogenetic: 12q24.31 12: 123718616-123718620 (GRCh38) [ NCBI UCSC ] 12: 124203163-124203167 (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	Dec 16, 2018	Apr 1, 2023	Mar 23, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_012463.4:c.118-7_118-3del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000012.12:g.123718616_123718620del
NC_000012.11:g.124203163_124203167del
NG_012743.1:g.11299_11303del

Protein change

Other names

Canonical SPDI

NC_000012.12:123718615:TTCTC:

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.

Exome Aggregation Consortium (ExAC) 0.00006

The Genome Aggregation Database (gnomAD), exomes 0.00006

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Trans-Omics for Precision Medicine (TOPMed) 0.00008

The Genome Aggregation Database (gnomAD) 0.00013

Links

dbSNP: rs777322469 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.
ATP6V0A2		-	-	GRCh38 GRCh37	612	718

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	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Mar 23, 2023	RCV000729315.7
ALG9 congenital disorder of glycosylation	Uncertain significance (1)	criteria provided, single submitter	Jan 28, 2022	RCV001868941.3

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 (Oct 02, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000856965.1 First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP6V0A2 Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed
Uncertain significance (Jan 28, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	ALG9 congenital disorder of glycosylation Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002118764.2 First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023	Publications: PubMed (2) PubMed: 17576681‚ 9536098 Comment: This sequence change falls in intron 1 of the ATP6V0A2 gene. It does not directly change the encoded amino acid sequence of the ATP6V0A2 protein. … (more) This sequence change falls in intron 1 of the ATP6V0A2 gene. It does not directly change the encoded amino acid sequence of the ATP6V0A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs777322469, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 594101). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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)
Likely benign (Mar 23, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001765230.2 First in ClinVar: Aug 07, 2021 Last updated: Apr 01, 2023	Comment: See Variant Classification Assertion Criteria.

Comment:

This sequence change falls in intron 1 of the ATP6V0A2 gene. It does not directly change the encoded amino acid sequence of the ATP6V0A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs777322469, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ATP6V0A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 594101). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.

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
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP6V0A2	-	-	-	-

Text-mined citations for rs777322469 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_012463.4(ATP6V0A2):c.118-7_118-3del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs777322469 ...