NM_001613.4(ACTA2):c.305A>C (p.Glu102Ala) AND Aortic aneurysm, familial thoracic 6

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 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:: RCV003118505.4

Allele description

NM_001613.4(ACTA2):c.305A>C (p.Glu102Ala)

Gene:

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.305A>C (p.Glu102Ala)

HGVS:

NC_000010.11:g.88943861T>G
NG_011541.1:g.52530A>C
NM_001141945.3:c.305A>C
NM_001320855.2:c.305A>C
NM_001406462.1:c.305A>C
NM_001406463.1:c.305A>C
NM_001406464.1:c.305A>C
NM_001406467.1:c.176A>C
NM_001406468.1:c.176A>C
NM_001406469.1:c.176A>C
NM_001406471.1:c.305A>C
NM_001613.4:c.305A>CMANE SELECT
NP_001135417.1:p.Glu102Ala
NP_001135417.1:p.Glu102Ala
NP_001135417.1:p.Glu102Ala
NP_001307784.1:p.Glu102Ala
NP_001307784.1:p.Glu102Ala
NP_001393391.1:p.Glu102Ala
NP_001393392.1:p.Glu102Ala
NP_001393393.1:p.Glu102Ala
NP_001393396.1:p.Glu59Ala
NP_001393397.1:p.Glu59Ala
NP_001393398.1:p.Glu59Ala
NP_001393400.1:p.Glu102Ala
NP_001604.1:p.Glu102Ala
NP_001604.1:p.Glu102Ala
LRG_781t1:c.305A>C
LRG_781t2:c.305A>C
LRG_781:g.52530A>C
LRG_781p1:p.Glu102Ala
LRG_781p2:p.Glu102Ala
NC_000010.10:g.90703618T>G
NM_001141945.1:c.305A>C
NM_001141945.2:c.305A>C
NM_001320855.1:c.305A>C
NM_001613.2:c.305A>C

Protein change:

E102A

Molecular consequence:

NM_001141945.3:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001320855.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406462.1:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406463.1:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406464.1:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406467.1:c.176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406468.1:c.176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406469.1:c.176A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406471.1:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001613.4:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Aortic aneurysm, familial thoracic 6 (AAT6)
Synonyms:: FAMILIAL THORACIC AORTIC ANEURYSM WITH LIVEDO RETICULARIS AND IRIS FLOCCULI
Identifiers:: MONDO: MONDO:0012730; MedGen: C2673186; OMIM: 611788

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003786687	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003786687

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003786687.3

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

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ACTA2-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 102 of the ACTA2 protein (p.Glu102Ala).

#	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: Feb 20, 2024

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