rs10496228

Variant names:

• chr2-79477990-A-G
• rs10496228
• NM_001399737.1:c.-134-27064A>G

Variant summary

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

The NM_001399737.1(CTNNA2):​c.-134-27064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,092 control chromosomes in the GnomAD database, including 26,242 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 0.58 (26242 hom., cov: 33)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• 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 (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001399737.1	c.-134-27064A>G		intron_variant	Intron 4 of 21		NP_001386666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-134-27064A>G		intron_variant	Intron 4 of 21	2		ENSP00000418191.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87763 AN: 151974 Hom.: 26235 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.577 AC: 87810 AN: 152092 Hom.: 26242 Cov.: 33 AF XY: 0.574 AC XY: 42677 AN XY: 74332

African (AFR) AF: 0.424 AC: 17608 AN: 41486

American (AMR) AF: 0.596 AC: 9099 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2411 AN: 5166

South Asian (SAS) AF: 0.498 AC: 2400 AN: 4824

European-Finnish (FIN) AF: 0.667 AC: 7051 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44777 AN: 67990

Other (OTH) AF: 0.590 AC: 1248 AN: 2114

Alfa AF: 0.610 Hom.: 3717

Bravo AF: 0.572

Asia WGS AF: 0.490 AC: 1708 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	4.0
DANN	Benign	0.76
PhyloP100		0.41
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: rs10496228; hg19: chr2-79705116;