2-80446489-C-T

Variant names:

• chr2-80446489-C-T
• rs1444543
• NM_001282597.3:c.1290+26888C>T

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1290+26888C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,150 control chromosomes in the GnomAD database, including 18,254 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 0.40 (18254 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1290+26888C>T		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.1290+26888C>T		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61355 AN: 152034 Hom.: 18201 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.404 AC: 61471 AN: 152150 Hom.: 18254 Cov.: 33 AF XY: 0.407 AC XY: 30266 AN XY: 74388

African (AFR) AF: 0.810 AC: 33613 AN: 41508

American (AMR) AF: 0.383 AC: 5843 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3468

East Asian (EAS) AF: 0.748 AC: 3871 AN: 5176

South Asian (SAS) AF: 0.282 AC: 1360 AN: 4824

European-Finnish (FIN) AF: 0.246 AC: 2605 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12680 AN: 68000

Other (OTH) AF: 0.360 AC: 760 AN: 2110

Alfa AF: 0.256 Hom.: 31219

Bravo AF: 0.436

Asia WGS AF: 0.540 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.68
PhyloP100		-0.52
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: rs1444543; hg19: chr2-80673614;