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NM_001613.4(ACTA2):c.720G>C (p.Lys240Asn) AND Aortic aneurysm, familial thoracic 6

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 17, 2019
Review status:
criteria provided, conflicting classifications
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:
RCV000622410.16

Allele description [Variation Report for NM_001613.4(ACTA2):c.720G>C (p.Lys240Asn)]

NM_001613.4(ACTA2):c.720G>C (p.Lys240Asn)

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.720G>C (p.Lys240Asn)
HGVS:
  • NC_000010.11:g.88939595C>G
  • NG_011541.1:g.56796G>C
  • NM_001141945.3:c.720G>C
  • NM_001320855.2:c.720G>C
  • NM_001406462.1:c.720G>C
  • NM_001406463.1:c.720G>C
  • NM_001406464.1:c.720G>C
  • NM_001406466.1:c.609G>C
  • NM_001406467.1:c.591G>C
  • NM_001406468.1:c.591G>C
  • NM_001406469.1:c.591G>C
  • NM_001613.4:c.720G>CMANE SELECT
  • NP_001135417.1:p.Lys240Asn
  • NP_001135417.1:p.Lys240Asn
  • NP_001135417.1:p.Lys240Asn
  • NP_001307784.1:p.Lys240Asn
  • NP_001307784.1:p.Lys240Asn
  • NP_001393391.1:p.Lys240Asn
  • NP_001393392.1:p.Lys240Asn
  • NP_001393393.1:p.Lys240Asn
  • NP_001393395.1:p.Lys203Asn
  • NP_001393396.1:p.Lys197Asn
  • NP_001393397.1:p.Lys197Asn
  • NP_001393398.1:p.Lys197Asn
  • NP_001604.1:p.Lys240Asn
  • NP_001604.1:p.Lys240Asn
  • LRG_781t1:c.720G>C
  • LRG_781t2:c.720G>C
  • LRG_781:g.56796G>C
  • LRG_781p1:p.Lys240Asn
  • LRG_781p2:p.Lys240Asn
  • NC_000010.10:g.90699352C>G
  • NM_001141945.1:c.720G>C
  • NM_001141945.2:c.720G>C
  • NM_001320855.1:c.720G>C
  • NM_001613.2:c.720G>C
  • NR_125373.1:n.1664C>G
Protein change:
K197N
Links:
dbSNP: rs727502878
NCBI 1000 Genomes Browser:
rs727502878
Molecular consequence:
  • NM_001141945.3:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320855.2:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406462.1:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406463.1:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406464.1:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406466.1:c.609G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406467.1:c.591G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406468.1:c.591G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406469.1:c.591G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001613.4:c.720G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_125373.1:n.1664C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000938949Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 17, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000938949.7

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

Description

This sequence change replaces lysine with asparagine at codon 240 of the ACTA2 protein (p.Lys240Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in a family affected with thoracic aortic aneurysm and dissection (Invitae). ClinVar contains an entry for this variant (Variation ID: 162701). This variant is not present in population databases (ExAC no frequency).

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

Last Updated: May 3, 2025