2-80488024-T-G

Position:

• chr2-80488024-T-G

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1291-56958T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,092 control chromosomes in the GnomAD database, including 9,316 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 (9316 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1291-56958T>G		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-56958T>G		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52033 AN: 151974 Hom.: 9307 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.342 AC: 52076 AN: 152092 Hom.: 9316 Cov.: 32 AF XY: 0.347 AC XY: 25783 AN XY: 74352

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.379

Alfa AF: 0.316 Hom.: 4661

Bravo AF: 0.353

Asia WGS AF: 0.532 AC: 1844 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.77

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: rs7600563; hg19: chr2-80715149;