rs6547311

Positions:

• chr2-80483835-G-C

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1291-61147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,984 control chromosomes in the GnomAD database, including 7,568 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 (7568 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-61147G>C		intron_variant		ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-61147G>C		intron_variant		1	NM_001282597.3	ENSP00000384638

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45723 AN: 151866 Hom.: 7552 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.301 AC: 45784 AN: 151984 Hom.: 7568 Cov.: 32 AF XY: 0.309 AC XY: 22919 AN XY: 74290

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.307

Alfa AF: 0.271 Hom.: 728

Bravo AF: 0.313

Asia WGS AF: 0.551 AC: 1911 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.73

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: rs6547311; hg19: chr2-80710960;