rs2010574

Variant names:

• chr2-80586074-G-A
• rs2010574
• NM_001282597.3:c.2008-3230G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CTNNA2 Gene-Disease associations (from GenCC):

• cortical dysplasia, complex, with other brain malformations 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000237031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282597.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.2008-3230G>A		intron	N/A	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.2110-3230G>A		intron	N/A	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.2008-3230G>A		intron	N/A	NP_001386666.1	P26232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.2008-3230G>A		intron	N/A	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.2008-3230G>A		intron	N/A	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000343114.7	TSL:1	c.1045-3230G>A		intron	N/A	ENSP00000341500.3	P26232-6

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

African (AFR) AF: 0.667 AC: 27641 AN: 41448

American (AMR) AF: 0.569 AC: 8671 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1762 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3371 AN: 5160

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5311 AN: 10552

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35036 AN: 67968

Other (OTH) AF: 0.587 AC: 1237 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.59
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2010574; hg19: chr2-80813199;