rs12471455

Variant names:

• chr2-79683223-G-A
• rs12471455
• NM_001282597.3:c.102+31565G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282597.3(CTNNA2):​c.102+31565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,224 control chromosomes in the GnomAD database, including 605 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 0.085 (605 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• cortical dysplasia, complex, with other brain malformations 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.102+31565G>A		intron_variant	Intron 2 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.102+31565G>A		intron_variant	Intron 2 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12895 AN: 152106 Hom.: 605 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0848 AC: 12911 AN: 152224 Hom.: 605 Cov.: 33 AF XY: 0.0834 AC XY: 6208 AN XY: 74424

African (AFR) AF: 0.102 AC: 4217 AN: 41538

American (AMR) AF: 0.0665 AC: 1017 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3472

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5170

South Asian (SAS) AF: 0.123 AC: 595 AN: 4826

European-Finnish (FIN) AF: 0.0783 AC: 830 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5417 AN: 68004

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.0812 Hom.: 855

Bravo AF: 0.0823

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.56
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12471455; hg19: chr2-79910349;