rs17019225

chr2-80488259-T-Achr2-80488259-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282597.3(CTNNA2):c.1291-56723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,124 control chromosomes in the GnomAD database, including 6,848 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6848 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1291-56723T>A		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-56723T>A		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42143 AN: 152004 Hom.: 6846 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42155 AN: 152124 Hom.: 6848 Cov.: 32 AF XY: 0.282 AC XY: 21003 AN XY: 74368

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.331

Alfa AF: 0.152 Hom.: 280

Bravo AF: 0.281

Asia WGS AF: 0.490 AC: 1697 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.2
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs17019225; hg19: chr2-80715384;