2-80577159-G-A

Position:

• chr2-80577159-G-A

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1893+2845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,026 control chromosomes in the GnomAD database, including 26,700 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 0.59 (26700 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.1893+2845G>A		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1893+2845G>A		intron_variant		1	NM_001282597.3
	ENST00000609950.1	n.194-1874C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89737 AN: 151908 Hom.: 26683 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.591 AC: 89798 AN: 152026 Hom.: 26700 Cov.: 32 AF XY: 0.589 AC XY: 43800 AN XY: 74330

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.631

Alfa AF: 0.615 Hom.: 11133

Bravo AF: 0.589

Asia WGS AF: 0.547 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57

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: rs216617; hg19: chr2-80804284;