Genetic Variant CTNNA2:c.-6+9949A>G (chr2-79523156-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282597.3(CTNNA2):c.-6+9949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 359,794 control chromosomes in the GnomAD database, including 9,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4400 hom., cov: 32)

Exomes 𝑓: 0.22 ( 5440 hom. )

Consequence

CTNNA2
NM_001282597.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.961

Publications

1 publications found

Variant links:

Genes affected

CTNNA2 (HGNC:2510): (catenin alpha 2) Enables actin filament binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation; regulation of neuron migration; and regulation of neuron projection development. Located in cytoplasm. Implicated in complex cortical dysplasia with other brain malformations. [provided by Alliance of Genome Resources, Apr 2022]

CTNNA2 Gene-Disease associations (from GenCC):

cortical dysplasia, complex, with other brain malformations 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

CTNNA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-79523156-A-G is Benign according to our data. Variant chr2-79523156-A-G is described in ClinVar as [Benign]. Clinvar id is 1248104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3 link	c.-6+9949A>G		intron_variant	Intron 1 of 18	ENST00000402739.9	NP_001269526.1	P26232-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9 link	c.-6+9949A>G		intron_variant	Intron 1 of 18	1	NM_001282597.3	ENSP00000384638.4		P26232-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35321

AN:

151872

Hom.:

4397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.216

AC:

44887

AN:

207804

Hom.:

5440

AF XY:

0.225

AC XY:

26966

AN XY:

119900

show subpopulations

African (AFR)

AF:

0.299

AC:

1613

AN:

5398

American (AMR)

AF:

0.145

AC:

1957

AN:

13510

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

1989

AN:

7308

East Asian (EAS)

AF:

0.104

AC:

797

AN:

7674

South Asian (SAS)

AF:

0.291

AC:

11454

AN:

39412

European-Finnish (FIN)

AF:

0.169

AC:

1615

AN:

9554

Middle Eastern (MID)

AF:

0.394

AC:

927

AN:

2354

European-Non Finnish (NFE)

AF:

0.198

AC:

22371

AN:

112722

Other (OTH)

AF:

0.219

AC:

2164

AN:

9872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1524

3048

4572

6096

7620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.232

AC:

35337

AN:

151990

Hom.:

4400

Cov.:

AF XY:

0.231

AC XY:

17188

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.308

AC:

12772

AN:

41416

American (AMR)

AF:

0.187

AC:

2849

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

946

AN:

3464

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5164

South Asian (SAS)

AF:

0.285

AC:

1375

AN:

4818

European-Finnish (FIN)

AF:

0.168

AC:

1778

AN:

10578

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.208

AC:

14126

AN:

67976

Other (OTH)

AF:

0.255

AC:

538

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1380

2760

4139

5519

6899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.215

Hom.:

781

Bravo

AF:

0.235

Asia WGS

AF:

0.187

AC:

653

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.17

(source)

DANN

Benign

0.58

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr2-79523156-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over