dbSNP rs78677982: CTNNA2:c.102+138T>A (chr2-79651796-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001282597.3(CTNNA2):c.102+138T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 701,446 control chromosomes in the GnomAD database, including 6,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.087 ( 1017 hom., cov: 32)

Exomes 𝑓: 0.12 ( 5242 hom. )

Consequence

CTNNA2
NM_001282597.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.459

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-79651796-T-A is Benign according to our data. Variant chr2-79651796-T-A is described in ClinVar as [Benign]. Clinvar id is 1226238.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3 link	c.102+138T>A		intron_variant	Intron 2 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.102+138T>A		intron_variant	Intron 2 of 18	1	NM_001282597.3	ENSP00000384638.4		P26232-1

Frequencies

GnomAD3 genomes

AF:

0.0870

AC:

13244

AN:

152148

Hom.:

1011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0783

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0974

Gnomad OTH

AF:

0.0860

GnomAD4 exome

AF:

0.119

AC:

65109

AN:

549180

Hom.:

5242

AF XY:

0.124

AC XY:

35663

AN XY:

286956

show subpopulations

African (AFR)

AF:

0.0223

AC:

324

AN:

14552

American (AMR)

AF:

0.0441

AC:

979

AN:

22202

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

2953

AN:

15040

East Asian (EAS)

AF:

0.303

AC:

9586

AN:

31646

South Asian (SAS)

AF:

0.224

AC:

10571

AN:

47120

European-Finnish (FIN)

AF:

0.0790

AC:

2869

AN:

36294

Middle Eastern (MID)

AF:

0.119

AC:

436

AN:

3658

European-Non Finnish (NFE)

AF:

0.0966

AC:

33730

AN:

349322

Other (OTH)

AF:

0.125

AC:

3661

AN:

29346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2674

5348

8023

10697

13371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0870

AC:

13248

AN:

152266

Hom.:

1017

Cov.:

AF XY:

0.0882

AC XY:

6568

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0228

AC:

947

AN:

41574

American (AMR)

AF:

0.0582

AC:

890

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

737

AN:

3470

East Asian (EAS)

AF:

0.352

AC:

1820

AN:

5168

South Asian (SAS)

AF:

0.222

AC:

1070

AN:

4822

European-Finnish (FIN)

AF:

0.0783

AC:

831

AN:

10618

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0973

AC:

6619

AN:

68006

Other (OTH)

AF:

0.0885

AC:

187

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

591

1183

1774

2366

2957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0889

Hom.:

Bravo

AF:

0.0830

Asia WGS

AF:

0.234

AC:

814

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.80

CADD

Benign

4.0

(source)

DANN

Benign

0.64

PhyloP100

-0.46

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs78677982

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