VCV002506586.1 - ClinVar

NM_000020.3(ACVRL1):c.289_294del (p.His97_Asn98del)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000020.3(ACVRL1):c.289_294del (p.His97_Asn98del)

Variation ID: 2506586 Accession: VCV002506586.1

Type and length

Deletion, 6 bp

Location

Cytogenetic: 12q13.13 12: 51913322-51913327 (GRCh38) [ NCBI UCSC ] 12: 52307106-52307111 (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	Jul 1, 2023	Jul 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000020.3:c.289_294del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000011.2:p.His97_Asn98del	inframe deletion
NM_001077401.2:c.289_294del	NP_001070869.1:p.His97_Asn98del	inframe deletion
NM_001406487.1:c.289_294del	NP_001393416.1:p.His97_Asn98del	inframe deletion
NM_001406488.1:c.289_294del	NP_001393417.1:p.His97_Asn98del	inframe deletion
NM_001406489.1:c.289_294del	NP_001393418.1:p.His97_Asn98del	inframe deletion
NM_001406490.1:c.289_294del	NP_001393419.1:p.His97_Asn98del	inframe deletion
NM_001406491.1:c.289_294del	NP_001393420.1:p.His97_Asn98del	inframe deletion
NM_001406492.1:c.289_294del	NP_001393421.1:p.His97_Asn98del	inframe deletion
NM_001406493.1:c.289_294del	NP_001393422.1:p.His97_Asn98del	inframe deletion
NM_001406494.1:c.289_294del	NP_001393423.1:p.His97_Asn98del	inframe deletion
NM_001406495.1:c.61+791_61+796del		intron variant
NC_000012.12:g.51913326_51913331del
NC_000012.11:g.52307110_52307115del
NG_009549.1:g.10909_10914del
NG_125717.1:g.104_109del
LRG_543:g.10909_10914del
LRG_543t1:c.289_294del	LRG_543p1:p.His97_Asn98del

... more HGVS ... less HGVS

Protein change

Other names

chr12-51913321 GCAACCA>G

Canonical SPDI

NC_000012.12:51913321:CAACCACAAC:CAAC

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.
ACVRL1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1011	1022

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.
Telangiectasia, hereditary hemorrhagic, type 2	Pathogenic (1)	criteria provided, single submitter	-	RCV003236766.1

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.
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Telangiectasia, hereditary hemorrhagic, type 2 (Autosomal dominant inheritance) Affected status: yes Allele origin: inherited	HHT Research Lab - C. Olivieri, University Of Pavia Accession: SCV003935205.1 First in ClinVar: Jul 01, 2023 Last updated: Jul 01, 2023	Publications: PubMed (1) PubMed: 35620871 Comment: This in frame deletion variant in ACVRL1 was founded in 66 subjects showing clinical signs of HHT. Other 22 unaffected relatives were tested to test … (more) This in frame deletion variant in ACVRL1 was founded in 66 subjects showing clinical signs of HHT. Other 22 unaffected relatives were tested to test the effective co-segregation of the variant with the disease. These 88 individuals belong to 19 different families. For this variant was demonstrated an Italian Founder effect. PMID: 35620871 (less) Number of individuals with the variant: 66 Sex: mixed Ethnicity/Population group: European Geographic origin: Italy, Bergamo province

Comment:

This in frame deletion variant in ACVRL1 was founded in 66 subjects showing clinical signs of HHT. Other 22 unaffected relatives were tested to test the effective co-segregation of the variant with the disease. These 88 individuals belong to 19 different families. For this variant was demonstrated an Italian Founder effect. PMID: 35620871

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
Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.	Sbalchiero A	Molecular genetics & genomic medicine	2022	PMID: 35620871

Text-mined citations for this variant ...

Record last updated Jul 01, 2023

ClinVar Genomic variation as it relates to human health

NM_000020.3(ACVRL1):c.289_294del (p.His97_Asn98del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...