VCV000464866.13 - ClinVar

NM_002890.3(RASA1):c.3109_3112del (p.Gln1037fs)

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.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002890.3(RASA1):c.3109_3112del (p.Gln1037fs)

Variation ID: 464866 Accession: VCV000464866.13

Type and length

Deletion, 4 bp

Location

Cytogenetic: 5q14.3 5: 87390845-87390848 (GRCh38) [ NCBI UCSC ] 5: 86686662-86686665 (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	Oct 10, 2018	Feb 14, 2024	May 23, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_002890.3:c.3109_3112del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002881.1:p.Gln1037fs	frameshift
NM_001363539.2:c.2012_2015del		3 prime UTR
NM_001364075.2:c.933+4196_933+4199del		intron variant
NM_001364076.2:c.2012_2015del		3 prime UTR
NM_002890.2:c.3109_3112del
NM_022650.3:c.2578_2581del	NP_072179.1:p.Gln860fs	frameshift
NR_157071.2:n.2962_2965del		non-coding transcript variant
NC_000005.10:g.87390848_87390851del
NC_000005.9:g.86686665_86686668del
NG_011650.1:g.127515_127518del

... more HGVS ... less HGVS

Protein change

Q860fs, Q1037fs

Other names

Canonical SPDI

NC_000005.10:87390844:AAACAAA:AAA

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

ClinGen: CA658657462 dbSNP: rs1554051094 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.
RASA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	293	1328
CCNH		-	-	GRCh38 GRCh37	22	1058

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.
Capillary malformation-arteriovenous malformation syndrome	Likely pathogenic (1)	criteria provided, single submitter	Jun 21, 2021	RCV000546260.20
Capillary malformation-arteriovenous malformation 1	Uncertain significance (1)	criteria provided, single submitter	May 23, 2022	RCV003133316.10

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 23, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Capillary malformation-arteriovenous malformation 1 Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003813773.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Likely pathogenic (Jun 21, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Capillary malformation-arteriovenous malformation syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000639545.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 28492532‚ 24038909 Comment: In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more) In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the frameshift is currently unknown. This variant has been reported to segregate with capillary malformation-arteriovenous malformation in a family (PMID: 24038909). This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the last exon of the RASA1 gene (p.Gln1037Thrfs*63). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acids of the RASA1 protein, and to extend the protein by an additional 52 amino acids. (less)

Comment:

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the frameshift is currently unknown. This variant has been reported to segregate with capillary malformation-arteriovenous malformation in a family (PMID: 24038909). This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the last exon of the RASA1 gene (p.Gln1037Thrfs*63). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acids of the RASA1 protein, and to extend the protein by an additional 52 amino acids.

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
RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.	Revencu N	Human mutation	2013	PMID: 24038909

Text-mined citations for rs1554051094 ...

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 Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_002890.3(RASA1):c.3109_3112del (p.Gln1037fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1554051094 ...