rs1971117

chr2-80486359-C-Gchr2-80486359-C-T

Variant summary

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

The NM_001282597.3(CTNNA2):c.1291-58623C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,966 control chromosomes in the GnomAD database, including 9,380 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 0.34 (9380 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1291-58623C>G		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-58623C>G		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52328 AN: 151850 Hom.: 9371 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.345 AC: 52370 AN: 151966 Hom.: 9380 Cov.: 32 AF XY: 0.349 AC XY: 25889 AN XY: 74260

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.375

Alfa AF: 0.174 Hom.: 300

Bravo AF: 0.356

Asia WGS AF: 0.531 AC: 1844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.98
Dann	Benign	0.75

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: rs1971117; hg19: chr2-80713484;