2-79430212-A-G

Position:

• chr2-79430212-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399737.1(CTNNA2):​c.-135+56199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,848 control chromosomes in the GnomAD database, including 18,351 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 0.48 (18351 hom., cov: 32)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001399737.1	c.-135+56199A>G		intron_variant			NP_001386666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-135+56199A>G		intron_variant		2		ENSP00000418191	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72922 AN: 151730 Hom.: 18323 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.481 AC: 73010 AN: 151848 Hom.: 18351 Cov.: 32 AF XY: 0.486 AC XY: 36045 AN XY: 74184

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.481

Alfa AF: 0.415 Hom.: 12726

Bravo AF: 0.485

Asia WGS AF: 0.601 AC: 2083 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.72

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: rs6722266; hg19: chr2-79657338;