NM_001399737.1:c.-134-22826C>T

Variant names:

• chr2-79482228-C-T
• rs7570469
• NM_001399737.1:c.-134-22826C>T

Variant summary

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

The NM_001399737.1(CTNNA2):​c.-134-22826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,038 control chromosomes in the GnomAD database, including 25,692 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 0.57 (25692 hom., cov: 33)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 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.-134-22826C>T		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.-134-22826C>T		intron	N/A	ENSP00000418191.1	P26232-2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86454 AN: 151918 Hom.: 25687 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.569 AC: 86492 AN: 152038 Hom.: 25692 Cov.: 33 AF XY: 0.566 AC XY: 42065 AN XY: 74322

African (AFR) AF: 0.397 AC: 16444 AN: 41464

American (AMR) AF: 0.591 AC: 9021 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2341 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2398 AN: 5150

South Asian (SAS) AF: 0.497 AC: 2392 AN: 4814

European-Finnish (FIN) AF: 0.668 AC: 7067 AN: 10578

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

European-Non Finnish (NFE) AF: 0.658 AC: 44731 AN: 67984

Other (OTH) AF: 0.583 AC: 1233 AN: 2114

Alfa AF: 0.630 Hom.: 88369

Bravo AF: 0.562

Asia WGS AF: 0.492 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.0
DANN	Benign	0.54
PhyloP100		1.1
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: rs7570469; hg19: chr2-79709354;