rs12611756

Positions:

• chr2-80534067-A-C
• chr2-80534067-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282597.3(CTNNA2):​c.1291-10915A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,010 control chromosomes in the GnomAD database, including 36,844 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 0.69 (36844 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1291-10915A>C		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-10915A>C		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104336 AN: 151892 Hom.: 36795 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.687 AC: 104442 AN: 152010 Hom.: 36844 Cov.: 32 AF XY: 0.686 AC XY: 51006 AN XY: 74300

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.621

Alfa AF: 0.638 Hom.: 56208

Bravo AF: 0.684

Asia WGS AF: 0.609 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.69

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: rs12611756; hg19: chr2-80761192;