2-80450185-T-C

Variant summary

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

The NM_001282597.3(CTNNA2):c.1290+30584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,018 control chromosomes in the GnomAD database, including 18,168 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 0.45 (18168 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1290+30584T>C		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1290+30584T>C		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68711 AN: 151902 Hom.: 18112 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.453 AC: 68833 AN: 152018 Hom.: 18168 Cov.: 33 AF XY: 0.459 AC XY: 34099 AN XY: 74288

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.428

Alfa AF: 0.184 Hom.: 322

Bravo AF: 0.479

Asia WGS AF: 0.647 AC: 2240 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.26
Dann	Benign	0.59

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: rs7609261; hg19: chr2-80677310;