rs12616530

Variant names:

• chr2-79477914-T-C
• rs12616530
• NM_001399737.1:c.-134-27140T>C

Variant summary

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

The NM_001399737.1(CTNNA2):​c.-134-27140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,050 control chromosomes in the GnomAD database, including 26,260 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 (26260 hom., cov: 33)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399737.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001399737.1		c.-134-27140T>C		intron	N/A	NP_001386666.1	P26232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000466387.5	TSL:2	c.-134-27140T>C		intron	N/A	ENSP00000418191.1	P26232-2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87798 AN: 151930 Hom.: 26252 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.668

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: 0.578 AC: 87847 AN: 152050 Hom.: 26260 Cov.: 33 AF XY: 0.575 AC XY: 42693 AN XY: 74308

African (AFR) AF: 0.425 AC: 17636 AN: 41476

American (AMR) AF: 0.596 AC: 9094 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2416 AN: 5170

South Asian (SAS) AF: 0.498 AC: 2404 AN: 4826

European-Finnish (FIN) AF: 0.668 AC: 7061 AN: 10570

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

European-Non Finnish (NFE) AF: 0.659 AC: 44772 AN: 67970

Other (OTH) AF: 0.590 AC: 1247 AN: 2112

Alfa AF: 0.611 Hom.: 3723

Bravo AF: 0.573

Asia WGS AF: 0.495 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.46
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: rs12616530; hg19: chr2-79705040;