2-80486359-C-G

Variant names:

• chr2-80486359-C-G
• rs1971117
• NM_001282597.3:c.1291-58623C>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.1291-58623C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,966 control chromosomes in the GnomAD database, including 9,380 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 0.34 (9380 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-58623C>G		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.1291-58623C>G		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52328 AN: 151850 Hom.: 9371 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.345 AC: 52370 AN: 151966 Hom.: 9380 Cov.: 32 AF XY: 0.349 AC XY: 25889 AN XY: 74260

African (AFR) AF: 0.330 AC: 13684 AN: 41460

American (AMR) AF: 0.408 AC: 6213 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3187 AN: 5148

South Asian (SAS) AF: 0.511 AC: 2463 AN: 4822

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10568

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

European-Non Finnish (NFE) AF: 0.320 AC: 21758 AN: 67938

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.174 Hom.: 300

Bravo AF: 0.356

Asia WGS AF: 0.531 AC: 1844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.98
DANN	Benign	0.75
PhyloP100		-0.66
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: rs1971117; hg19: chr2-80713484;