NM_000020.3(ACVRL1):c.760_762del (p.Asp254del) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 2, 2022
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:: RCV002390098.9

Allele description [Variation Report for NM_000020.3(ACVRL1):c.760_762del (p.Asp254del)]

NM_000020.3(ACVRL1):c.760_762del (p.Asp254del)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.760_762del (p.Asp254del)

HGVS:

NC_000012.12:g.51914573_51914575del
NG_009549.1:g.12156_12158del
NM_000020.3:c.760_762delMANE SELECT
NM_001077401.2:c.760_762del
NP_000011.2:p.Asp254del
NP_001070869.1:p.Asp254del
LRG_543t1:c.760_762del
LRG_543:g.12156_12158del
NC_000012.11:g.52308355_52308357del
NC_000012.11:g.52308357_52308359del
NM_000020.2:c.760_762del
NM_000020.2:c.760_762delGAC

Protein change:

D254del

Links:

OMIM: 601284.0008; dbSNP: rs387906393

NCBI 1000 Genomes Browser:

rs387906393

Molecular consequence:

NM_000020.3:c.760_762del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001077401.2:c.760_762del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
gi|1519315772|ref|NM_031904.5|

Nucleotide
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
gi|1705442040|ref|NM_003724.4|

Nucleotide
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
gi|1957933713|gnl|PRJNA680355|I5Q86 5|gb|QQQ93614.1|

Protein
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
gi|1015828636|gb|AMW76581.1||gnl|PR 2950|JCVISYN3_0620

Protein
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clon...
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clone TBK01A01NGRL0077_4_C06 5', mRNA sequence
gi|254604633|gnl|dbEST|66633142|dbj 0464.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002675267	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 2, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11484689, 12114496, 14684682, 17384219, 21158752, 26387786, 32300199 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002675267

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 2, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.

Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L.

N Engl J Med. 2001 Aug 2;345(5):325-34.

PubMed [citation]

PMID:: 11484689

Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia.

Olivieri C, Mira E, Delù G, Pagella F, Zambelli A, Malvezzi L, Buscarini E, Danesino C.

J Med Genet. 2002 Jul;39(7):E39. No abstract available.

PubMed [citation]

PMID:: 12114496
PMCID:: PMC1735165

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002675267.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The c.760_762delGAC variant (also known as p.D254del) is located in coding exon 5 of the ACVRL1 gene. This variant results from an in-frame deletion of GAC between nucleotide positions 760 and 762. This results in the deletion of an aspartic acid residue at codon 254. In one study, this variant was detected in one HHT family and was found to segregate with disease (Trembath RC, et al. N. Engl. J. Med. 2001 Aug; 345(5):325-34). In addition, this variant was reported in an individual with epistaxis, telangiectasias, a hepatic ateriovenous malformation, and a family history of HHT (McDonald J, et al. Clin. Genet. 2011 Apr; 79(4):335-44). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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