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Brain Small Vessel Disease 2 via the COL4A2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
COL4A2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15129COL4A281479 81479,81479 $990 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

COL4A2-related brain small vessel disease 2 a rare neurological disorder that affects the small, deep, penetrating arteries and arterioles of the brain. The age onset is variable, ranging from prenatal to adult onset. The major symptoms include lacunar ischemic strokes, hemiplegia, spasticity, cerebral palsy, seizures, intellectual disability, and leukoencephalopathy. Brain MRI shows deep intracerebral hemorrhages, porencephaly, intracranial aneurysms, and reduced white matter volume. The minor features include cognitive impairment, memory loss, and ophthalmological signs (Jeanne and Gould. 2017. PubMed ID: 27794444; Ha et al. 2016. PubMed ID: 26708157; Gunda et al. 2014. PubMed ID: 24390199; Cavallin et al. 2018. PubMed ID: 30315939).

As brain small vessel disease can be caused by defects in many genes with variable and overlapping presentations, it is difficult to diagnose by clinical manifestation and image studies only. An accurate molecular diagnosis is critical for treatment, prognosis, and prediction of recurrence risk as well as future family planning.


COL4A2-related brain small vessel disease 2 is inherited in an autosomal dominant manner. The vast majority of pathogenic variants in COL4A2 are missense variants at conserved Gly residues in the Gly-X-Y repeats of the triple-helical domain, leading to alterations of the α1α1α2 heterotrimers (Human Gene Mutation Database; Fidler et al. 2018. PubMed ID: 29632050). Only a few truncating variants, including splicing and a small frameshift deletion, have been reported. A large deletion has also been reported at the COL4A2 locus (HGMD). De novo pathogenic variants are common and the disorder has variable severity with incomplete penetrance (Yoneda et al. 2012. PubMed ID: 22209246).

COL4A2 encodes the alpha-2 chain of type IV collagen. COL4A2 combined another subunit COL4A1 forms heterotrimers with 1:2 stoichiometry (alpha-1/alpha-1/alpha-2). Type IV collagen is then associated with laminin, entactin, and heparan sulfate proteoglycans to form basement membranes that separate epithelium from connective tissue (Jeanne and Gould. 2017. PubMed ID: 27794444). A mouse model heterozygous for the Col4a2 p.Gly646Asp variant showed complete penetrance of intracerebral hemorrhage and the retention of COL4A1/COL4A2 heterotrimers within the endoplasmic reticulum (Jeanne et al. 2012. PubMed ID: 22209247).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity of COL4A2 testing is high. However, brain small vessel disease caused by defects in COL4A2 is rare (Rannikmäe et al. 2015. PubMed ID: 25653287).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the COL4A2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

COL4A2 sequencing is recommended for patients suspected to have brain small vessel disease 2. Targeted testing is indicated for family members of patients who have a known pathogenic variant in COL4A2.


Official Gene Symbol OMIM ID
COL4A2 120090
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Porencephaly 2 AD 614483


  • Cavallin et al. 2018. PubMed ID: 30315939
  • Fidler et al. 2018. PubMed ID: 29632050
  • Gunda et al. 2014. PubMed ID: 24390199
  • Ha et al. 2016. PubMed ID: 26708157
  • Human Gene Mutation Database (Biobase).
  • Jeanne and Gould. 2017. PubMed ID: 27794444
  • Jeanne et al. 2012. PubMed ID: 22209247
  • Rannikmäe et al. 2015. PubMed ID: 25653287
  • Yoneda et al. 2012. PubMed ID: 22209246


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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