rs6742029

Variant names:

• chr2-80489566-G-A
• rs6742029
• NM_001282597.3:c.1291-55416G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282597.3(CTNNA2):​c.1291-55416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,998 control chromosomes in the GnomAD database, including 7,862 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 0.30 (7862 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-55416G>A		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.1291-55416G>A		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45580 AN: 151880 Hom.: 7860 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.300 AC: 45593 AN: 151998 Hom.: 7862 Cov.: 32 AF XY: 0.304 AC XY: 22593 AN XY: 74284

African (AFR) AF: 0.140 AC: 5806 AN: 41494

American (AMR) AF: 0.383 AC: 5836 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1591 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3044 AN: 5150

South Asian (SAS) AF: 0.481 AC: 2316 AN: 4810

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10578

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23273 AN: 67932

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.343 Hom.: 9309

Bravo AF: 0.302

Asia WGS AF: 0.501 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.54
PhyloP100		0.81
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: rs6742029; hg19: chr2-80716691;