U.S. flag

An official website of the United States government

NM_000020.3(ACVRL1):c.1377+1G>A AND Hereditary hemorrhagic telangiectasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 4, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003993880.1

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1377+1G>A]

NM_000020.3(ACVRL1):c.1377+1G>A

Gene:
ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000020.3(ACVRL1):c.1377+1G>A
HGVS:
  • NC_000012.12:g.51919116G>A
  • NG_009549.1:g.16699G>A
  • NM_000020.3:c.1377+1G>AMANE SELECT
  • NM_001077401.2:c.1377+1G>A
  • NM_001406487.1:c.1377+1G>A
  • NM_001406488.1:c.1378G>A
  • NM_001406489.1:c.1378G>A
  • NM_001406490.1:c.1221+1G>A
  • NM_001406491.1:c.1065+1G>A
  • NM_001406492.1:c.1065+1G>A
  • NM_001406493.1:c.1066G>A
  • NM_001406494.1:c.867+1G>A
  • NM_001406495.1:c.813+1G>A
  • NP_001393417.1:p.Val460Met
  • NP_001393418.1:p.Val460Met
  • NP_001393422.1:p.Val356Met
  • LRG_543t1:c.1377+1G>A
  • LRG_543:g.16699G>A
  • NC_000012.11:g.52312900G>A
  • NM_000020.2:c.1377+1G>A
Protein change:
V356M
Links:
dbSNP: rs863223406
NCBI 1000 Genomes Browser:
rs863223406
Molecular consequence:
  • NM_001406488.1:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406489.1:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406493.1:c.1066G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000020.3:c.1377+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001077401.2:c.1377+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406487.1:c.1377+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406490.1:c.1221+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406491.1:c.1065+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406492.1:c.1065+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406494.1:c.867+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406495.1:c.813+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary hemorrhagic telangiectasia (HHT)
Synonyms:
Osler Weber Rendu syndrome; ORW disease; Osler-Rendu-Weber disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019180; MedGen: C0039445; OMIM: PS187300

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004812860Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Sep 4, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.

Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M.

Hum Mutat. 2005 Mar;25(3):320.

PubMed [citation]
PMID:
15712270

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique.

Sadick H, Hage J, Goessler U, Stern-Straeter J, Riedel F, Hoermann K, Bugert P.

BMC Med Genet. 2009 Jun 9;10:53. doi: 10.1186/1471-2350-10-53.

PubMed [citation]
PMID:
19508727
PMCID:
PMC2701415
See all PubMed Citations (3)

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV004812860.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change in ACVRL1 occurs within the canonical splice donor site of intron 9. It is predicted to cause cryptic donor site activation resulting in an in-frame deletion (removes 19 amino acids) that is expected to remove part of the kinase domain which is critical for protein function. This variant is absent from the population database gnomAD v2.1 and v3.1. This variant has been reported in at least three probands meeting a clinical diagnosis of hereditary haemorrhagic telangiectasia (PMID: 15712270, 19508727; Royal Melbourne Hospital). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1_Strong, PM2_Supporting, PS4_Moderate

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024