NM_001282597.3:c.1291-15806T>C

Variant names:

• chr2-80529176-T-C
• rs17340143
• NM_001282597.3:c.1291-15806T>C

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1291-15806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,908 control chromosomes in the GnomAD database, including 14,848 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 0.44 (14848 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-15806T>C		intron_variant	Intron 9 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-15806T>C		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66968 AN: 151788 Hom.: 14848 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.441 AC: 67001 AN: 151908 Hom.: 14848 Cov.: 32 AF XY: 0.444 AC XY: 32959 AN XY: 74228

African (AFR) AF: 0.462 AC: 19132 AN: 41420

American (AMR) AF: 0.405 AC: 6177 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1969 AN: 5158

South Asian (SAS) AF: 0.568 AC: 2736 AN: 4820

European-Finnish (FIN) AF: 0.504 AC: 5316 AN: 10546

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29109 AN: 67928

Other (OTH) AF: 0.372 AC: 781 AN: 2102

Alfa AF: 0.428 Hom.: 44203

Bravo AF: 0.432

Asia WGS AF: 0.477 AC: 1658 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	2.4
DANN	Benign	0.45
PhyloP100		-0.19
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: rs17340143; hg19: chr2-80756301;