rs1484464

Variant names:

• chr2-80071408-G-A
• rs1484464
• NM_001282597.3:c.1056+161611G>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.1056+161611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,202 control chromosomes in the GnomAD database, including 54,895 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 0.84 (54895 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• 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=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1056+161611G>A		intron_variant	Intron 7 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1056+161611G>A		intron_variant	Intron 7 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.1056+161611G>A		intron_variant	Intron 7 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.1056+161611G>A		intron_variant	Intron 11 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.1056+161611G>A		intron_variant	Intron 7 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128367 AN: 152084 Hom.: 54841 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.844 AC: 128479 AN: 152202 Hom.: 54895 Cov.: 32 AF XY: 0.832 AC XY: 61861 AN XY: 74388

African (AFR) AF: 0.929 AC: 38588 AN: 41536

American (AMR) AF: 0.770 AC: 11766 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2876 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2498 AN: 5148

South Asian (SAS) AF: 0.741 AC: 3576 AN: 4828

European-Finnish (FIN) AF: 0.746 AC: 7906 AN: 10594

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58469 AN: 68020

Other (OTH) AF: 0.813 AC: 1713 AN: 2108

Alfa AF: 0.845 Hom.: 39855

Bravo AF: 0.850

Asia WGS AF: 0.639 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		1.4
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: rs1484464; hg19: chr2-80298534;