NM_001282597.3:c.1291-58965T>C

Variant names:

• chr2-80486017-T-C
• rs11126769
• NM_001282597.3:c.1291-58965T>C

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1291-58965T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,908 control chromosomes in the GnomAD database, including 9,340 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 0.34 (9340 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• Publications: 4 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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-58965T>C		intron_variant	Intron 9 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-58965T>C		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52141 AN: 151790 Hom.: 9331 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.344 AC: 52182 AN: 151908 Hom.: 9340 Cov.: 32 AF XY: 0.348 AC XY: 25801 AN XY: 74246

African (AFR) AF: 0.332 AC: 13751 AN: 41416

American (AMR) AF: 0.406 AC: 6196 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1505 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3183 AN: 5152

South Asian (SAS) AF: 0.511 AC: 2463 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2350 AN: 10552

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21568 AN: 67948

Other (OTH) AF: 0.373 AC: 783 AN: 2102

Alfa AF: 0.349 Hom.: 3918

Bravo AF: 0.356

Asia WGS AF: 0.532 AC: 1841 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.70
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: rs11126769; hg19: chr2-80713142;