rs2010574

Positions:

• chr2-80586074-G-A
• chr2-80586074-G-C
• chr2-80586074-G-T

Variant summary

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

The NM_001282597.3(CTNNA2):​c.2008-3230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,968 control chromosomes in the GnomAD database, including 24,570 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 0.56 (24570 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.2008-3230G>A		intron_variant		ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.2008-3230G>A		intron_variant		1	NM_001282597.3	ENSP00000384638
	ENST00000609950.1	n.194-10789C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85442 AN: 151850 Hom.: 24539 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.563 AC: 85526 AN: 151968 Hom.: 24570 Cov.: 32 AF XY: 0.561 AC XY: 41663 AN XY: 74274

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.587

Alfa AF: 0.544 Hom.: 3593

Bravo AF: 0.578

Asia WGS AF: 0.539 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.59

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: rs2010574; hg19: chr2-80813199;