Variant chr2-79651538-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282597.3(CTNNA2):c.-5-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,600,996 control chromosomes in the GnomAD database, including 35,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6730 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29003 hom. )

Consequence

CTNNA2
NM_001282597.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.47

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-79651538-A-G is Benign according to our data. Variant chr2-79651538-A-G is described in ClinVar as [Benign]. Clinvar id is 1255414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001282597.3 linkuse as main transcript	c.-5-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9 linkuse as main transcript	c.-5-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001282597.3	ENSP00000384638		P26232-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40080

AN:

151930

Hom.:

6696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.219

AC:

54537

AN:

248690

Hom.:

6986

AF XY:

0.215

AC XY:

28977

AN XY:

134920

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.188

AC:

273051

AN:

1448948

Hom.:

29003

Cov.:

AF XY:

0.189

AC XY:

136591

AN XY:

721668

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.264

AC:

40167

AN:

152048

Hom.:

6730

Cov.:

AF XY:

0.264

AC XY:

19622

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.179

Hom.:

1642

Bravo

AF:

0.280

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Cortical dysplasia, complex, with other brain malformations 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0040

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over