rs12472674

chr2-79950618-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282597.3(CTNNA2):c.1056+40821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,998 control chromosomes in the GnomAD database, including 21,552 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 0.52 (21552 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1056+40821C>T		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1056+40821C>T		intron_variant		1	NM_001282597.3
CTNNA2	ENST00000496558.5	c.1056+40821C>T		intron_variant		1		P1
CTNNA2	ENST00000466387.5	c.1056+40821C>T		intron_variant		2		P1
CTNNA2	ENST00000629316.2	c.1056+40821C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79334 AN: 151880 Hom.: 21557 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.522 AC: 79350 AN: 151998 Hom.: 21552 Cov.: 33 AF XY: 0.522 AC XY: 38778 AN XY: 74286

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.544

Alfa AF: 0.577 Hom.: 58852

Bravo AF: 0.522

Asia WGS AF: 0.563 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs12472674; hg19: chr2-80177744;