rs17019225

Variant names:

• chr2-80488259-T-A
• rs17019225
• NM_001282597.3:c.1291-56723T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-80488259-T-A
• chr2-80488259-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282597.3(CTNNA2):​c.1291-56723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,124 control chromosomes in the GnomAD database, including 6,848 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 0.28 (6848 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 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.1291-56723T>A		intron	N/A	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.1393-56723T>A		intron	N/A	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.1291-56723T>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.1291-56723T>A		intron	N/A	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.1291-56723T>A		intron	N/A	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000343114.7	TSL:1	c.328-56723T>A		intron	N/A	ENSP00000341500.3	P26232-6

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42143 AN: 152004 Hom.: 6846 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.277 AC: 42155 AN: 152124 Hom.: 6848 Cov.: 32 AF XY: 0.282 AC XY: 21003 AN XY: 74368

African (AFR) AF: 0.127 AC: 5287 AN: 41526

American (AMR) AF: 0.372 AC: 5686 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1706 AN: 3466

East Asian (EAS) AF: 0.587 AC: 3036 AN: 5174

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2300 AN: 10588

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20875 AN: 67970

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.152 Hom.: 280

Bravo AF: 0.281

Asia WGS AF: 0.490 AC: 1697 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.50
PhyloP100		0.15
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: rs17019225; hg19: chr2-80715384;