VCV001786575.2 - ClinVar

NM_000020.3(ACVRL1):c.214_219del (p.Leu72_His73del)

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.

Uncertain significance

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.214_219del (p.Leu72_His73del)

Variation ID: 1786575 Accession: VCV001786575.2

Type and length

Deletion, 6 bp

Location

Cytogenetic: 12q13.13 12: 51913249-51913254 (GRCh38) [ NCBI UCSC ] 12: 52307033-52307038 (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	Nov 29, 2022	May 1, 2024	Apr 18, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_000020.3:c.214_219del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000011.2:p.Leu72_His73del	inframe deletion
NM_001077401.2:c.214_219del	NP_001070869.1:p.Leu72_His73del	inframe deletion
NM_001406487.1:c.214_219delTTGCAC	NP_001393416.1:p.Leu72_His73del	inframe indel
NM_001406488.1:c.214_219delTTGCAC	NP_001393417.1:p.Leu72_His73del	inframe indel
NM_001406489.1:c.214_219delTTGCAC	NP_001393418.1:p.Leu72_His73del	inframe indel
NM_001406490.1:c.214_219delTTGCAC	NP_001393419.1:p.Leu72_His73del	inframe indel
NM_001406491.1:c.214_219delTTGCAC	NP_001393420.1:p.Leu72_His73del	inframe indel
NM_001406492.1:c.214_219delTTGCAC	NP_001393421.1:p.Leu72_His73del	inframe indel
NM_001406493.1:c.214_219delTTGCAC	NP_001393422.1:p.Leu72_His73del	inframe indel
NM_001406494.1:c.214_219delTTGCAC	NP_001393423.1:p.Leu72_His73del	inframe indel
NC_000012.12:g.51913251_51913256del
NC_000012.11:g.52307035_52307040del
NG_009549.1:g.10834_10839del
LRG_543:g.10834_10839del
LRG_543t1:c.214_219del	LRG_543p1:p.Leu72_His73del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000012.12:51913248:ACTTGCAC:AC

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.
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	Apr 18, 2018	RCV002430540.2

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 (Apr 18, 2018)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002729252.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 21158752 Comment: The c.214_219delTTGCAC variant (also known as p.L72_H73del) is located in coding exon 2 of the ACVRL1 gene. This variant results from an in-frame TTGCAC deletion … (more) The c.214_219delTTGCAC variant (also known as p.L72_H73del) is located in coding exon 2 of the ACVRL1 gene. This variant results from an in-frame TTGCAC deletion at nucleotide positions 214 to 219. This results in the in-frame deletion of two amino acids (leucine and histidine) at codons 72 and 73, which are not well conserved. This alteration was detected in an individual referred for hereditary hemorrhagic telangiectasia (HHT) genetic testing who had epistaxis and positive family history, and was indicated to also have another variant in an HHT-associated gene (McDonald J et al. Clin. Genet., 2011 Apr;79:335-44). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)

Comment:

The c.214_219delTTGCAC variant (also known as p.L72_H73del) is located in coding exon 2 of the ACVRL1 gene. This variant results from an in-frame TTGCAC deletion at nucleotide positions 214 to 219. This results in the in-frame deletion of two amino acids (leucine and histidine) at codons 72 and 73, which are not well conserved. This alteration was detected in an individual referred for hereditary hemorrhagic telangiectasia (HHT) genetic testing who had epistaxis and positive family history, and was indicated to also have another variant in an HHT-associated gene (McDonald J et al. Clin. Genet., 2011 Apr;79:335-44). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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
Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis.	McDonald J	Clinical genetics	2011	PMID: 21158752

Text-mined citations for this variant ...

Record last updated May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_000020.3(ACVRL1):c.214_219del (p.Leu72_His73del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...