Genetic Variant CTNNA2:c.-6+10210C>T (chr2-79523417-C-T) – 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+10210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 180,638 control chromosomes in the GnomAD database, including 39,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 32903 hom., cov: 32)

Exomes 𝑓: 0.65 ( 6204 hom. )

Consequence

CTNNA2
NM_001282597.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.111

Publications

2 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=-0.98).

BP6

Variant 2-79523417-C-T is Benign according to our data. Variant chr2-79523417-C-T is described in ClinVar as [Benign]. Clinvar id is 1243338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3 link	c.-6+10210C>T		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+10210C>T		intron_variant	Intron 1 of 18	1	NM_001282597.3	ENSP00000384638.4		P26232-1

Frequencies

GnomAD3 genomes

AF:

0.657

AC:

99811

AN:

151934

Hom.:

32873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.698

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.645

AC:

18443

AN:

28582

Hom.:

6204

AF XY:

0.647

AC XY:

11171

AN XY:

17272

show subpopulations

African (AFR)

AF:

0.606

AC:

355

AN:

586

American (AMR)

AF:

0.483

AC:

482

AN:

998

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

516

AN:

738

East Asian (EAS)

AF:

0.613

AC:

745

AN:

1216

South Asian (SAS)

AF:

0.630

AC:

2891

AN:

4590

European-Finnish (FIN)

AF:

0.682

AC:

1011

AN:

1482

Middle Eastern (MID)

AF:

0.603

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.657

AC:

11510

AN:

17518

Other (OTH)

AF:

0.646

AC:

845

AN:

1308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

313

626

940

1253

1566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.657

AC:

99891

AN:

152056

Hom.:

32903

Cov.:

AF XY:

0.655

AC XY:

48688

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.642

AC:

26634

AN:

41478

American (AMR)

AF:

0.572

AC:

8734

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2500

AN:

3470

East Asian (EAS)

AF:

0.661

AC:

3412

AN:

5158

South Asian (SAS)

AF:

0.655

AC:

3153

AN:

4814

European-Finnish (FIN)

AF:

0.698

AC:

7382

AN:

10576

Middle Eastern (MID)

AF:

0.613

AC:

179

AN:

292

European-Non Finnish (NFE)

AF:

0.674

AC:

45841

AN:

67968

Other (OTH)

AF:

0.648

AC:

1369

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1786

3572

5358

7144

8930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.559

Hom.:

1687

Bravo

AF:

0.647

Asia WGS

AF:

0.655

AC:

2281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.8

(source)

DANN

Benign

0.18

PhyloP100

0.11

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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2-79523417-C-T

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