2-80486017-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.1291-58965T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,908 control chromosomes in the GnomAD database, including 9,340 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 0.34 (9340 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1291-58965T>C		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-58965T>C		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52141 AN: 151790 Hom.: 9331 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.344 AC: 52182 AN: 151908 Hom.: 9340 Cov.: 32 AF XY: 0.348 AC XY: 25801 AN XY: 74246

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.373

Alfa AF: 0.336 Hom.: 2185

Bravo AF: 0.356

Asia WGS AF: 0.532 AC: 1841 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	16
Dann	Benign	0.82

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: rs11126769; hg19: chr2-80713142;