NM_001613.4(ACTA2):c.1132T>C (p.Ter378Gln) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001170187.4

Allele description [Variation Report for NM_001613.4(ACTA2):c.1132T>C (p.Ter378Gln)]

NM_001613.4(ACTA2):c.1132T>C (p.Ter378Gln)

Genes:

ACTA2-AS1:ACTA2 antisense RNA 1 [Gene - HGNC]
ACTA2:actin alpha 2, smooth muscle [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_001613.4(ACTA2):c.1132T>C (p.Ter378Gln)

Other names:

*378Q

HGVS:

NC_000010.11:g.88935225A>G
NG_011541.1:g.61166T>C
NM_001141945.3:c.1132T>C
NM_001320855.2:c.1132T>C
NM_001406462.1:c.1132T>C
NM_001406463.1:c.1132T>C
NM_001406464.1:c.1132T>C
NM_001406466.1:c.1021T>C
NM_001406467.1:c.1003T>C
NM_001406468.1:c.1003T>C
NM_001406469.1:c.1003T>C
NM_001406471.1:c.940T>C
NM_001613.4:c.1132T>CMANE SELECT
NP_001135417.1:p.Ter378Gln
NP_001135417.1:p.Ter378Gln
NP_001135417.1:p.Ter378Gln
NP_001307784.1:p.Ter378Gln
NP_001307784.1:p.Ter378Gln
NP_001393391.1:p.Ter378Gln
NP_001393392.1:p.Ter378Gln
NP_001393393.1:p.Ter378Gln
NP_001393395.1:p.Ter341Gln
NP_001393396.1:p.Ter335Gln
NP_001393397.1:p.Ter335Gln
NP_001393398.1:p.Ter335Gln
NP_001393400.1:p.Ter314Gln
NP_001604.1:p.Ter378Gln
NP_001604.1:p.Ter378Gln
LRG_781t1:c.1132T>C
LRG_781t2:c.1132T>C
LRG_781:g.61166T>C
LRG_781p1:p.Ter378Gln
LRG_781p2:p.Ter378Gln
NC_000010.10:g.90694982A>G
NM_001141945.1:c.1132T>C
NM_001141945.2:c.1132T>C
NM_001320855.1:c.1132T>C
NM_001613.2:c.1132T>C
NR_125373.1:n.850A>G

Links:

dbSNP: rs878854465

NCBI 1000 Genomes Browser:

rs878854465

Molecular consequence:

NR_125373.1:n.850A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001141945.3:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001320855.2:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406462.1:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406463.1:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406464.1:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406466.1:c.1021T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406467.1:c.1003T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406468.1:c.1003T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406469.1:c.1003T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001406471.1:c.940T>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001613.4:c.1132T>C - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001332737	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003998740	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Mar 20, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001332737

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 14, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003998740

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Mar 20, 2023)

germline

clinical testing

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001332737.1

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

#	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

From Ambry Genetics, SCV003998740.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.1132T>C variant (also known as p.*378Qext*14), located in coding exon 8 of the ACTA2 gene, results from a T to C substitution at nucleotide position 1132. This alteration disrupts the stop codon of the ACTA2 gene and is predicted to preserve the native sequence while resulting in the elongation of the protein by 14 amino acids. The exact functional effect of the additional amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Mar 10, 2024

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