NM_001282597.3:c.1291-59911A>G

Variant names:

• chr2-80485071-A-G
• rs6547313
• NM_001282597.3:c.1291-59911A>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.1291-59911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,876 control chromosomes in the GnomAD database, including 14,790 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 0.42 (14790 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• 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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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 (EAS) allele frequency at 95% confidence interval = 0.663 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.1291-59911A>G		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.1393-59911A>G		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.1291-59911A>G		intron	N/A	NP_001386666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.1291-59911A>G		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.1291-59911A>G		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000343114.7	TSL:1	c.328-59911A>G		intron	N/A	ENSP00000341500.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63027 AN: 151760 Hom.: 14765 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.415 AC: 63098 AN: 151876 Hom.: 14790 Cov.: 32 AF XY: 0.416 AC XY: 30906 AN XY: 74228

African (AFR) AF: 0.599 AC: 24772 AN: 41380

American (AMR) AF: 0.475 AC: 7242 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3513 AN: 5150

South Asian (SAS) AF: 0.511 AC: 2460 AN: 4810

European-Finnish (FIN) AF: 0.203 AC: 2148 AN: 10556

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20357 AN: 67936

Other (OTH) AF: 0.409 AC: 862 AN: 2106

Alfa AF: 0.346 Hom.: 3471

Bravo AF: 0.447

Asia WGS AF: 0.586 AC: 2034 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	0.66
DANN	Benign	0.55
PhyloP100		-0.16
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: rs6547313; hg19: chr2-80712196;