VCV001810198.2 - ClinVar

NM_024570.4(RNASEH2B):c.322-17A>G

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.

(2)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024570.4(RNASEH2B):c.322-17A>G

Variation ID: 1810198 Accession: VCV001810198.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q14.3 13: 50934868 (GRCh38) [ NCBI UCSC ] 13: 51509004 (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 7, 2023	Feb 14, 2024	Jun 30, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_024570.4:c.322-17A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001142279.2:c.322-17A>G		intron variant
NC_000013.11:g.50934868A>G
NC_000013.10:g.51509004A>G
NG_009055.1:g.30113A>G
LRG_279:g.30113A>G
LRG_279t1:c.322-17A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000013.11:50934867:A:G

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.
RNASEH2B		-	-	GRCh38 GRCh37	433	552

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.
Aicardi-Goutieres syndrome 2	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jun 30, 2023	RCV002508753.3

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 (May 20, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Aicardi-Goutieres syndrome 2 Affected status: yes Allele origin: germline	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital Accession: SCV002818104.1 First in ClinVar: Jan 07, 2023 Last updated: Jan 07, 2023	Comment: [ACMG/AMP: PM2, PM3] This alteration is absent from or rarely observed in large-scale population databases [PM2] and is detected in trans with a known pathogenic … (more) [ACMG/AMP: PM2, PM3] This alteration is absent from or rarely observed in large-scale population databases [PM2] and is detected in trans with a known pathogenic variant [PM3]. (less)
Uncertain significance (Jun 30, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Aicardi-Goutieres syndrome 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004297238.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 24183309 Comment: This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 4 of the RNASEH2B gene. It does … (more) This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 4 of the RNASEH2B gene. It does not directly change the encoded amino acid sequence of the RNASEH2B protein. This variant has been observed in individual(s) with RNASEH2B-related conditions (PMID: 24183309). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1810198). (less)

Comment:

This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 4 of the RNASEH2B gene. It does not directly change the encoded amino acid sequence of the RNASEH2B protein. This variant has been observed in individual(s) with RNASEH2B-related conditions (PMID: 24183309). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1810198).

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
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.	Rice GI	The Lancet. Neurology	2013	PMID: 24183309

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_024570.4(RNASEH2B):c.322-17A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...