NM_001282597.3:c.852+13567G>A

Variant names:

• chr2-79887909-G-A
• rs17018086
• NM_001282597.3:c.852+13567G>A

Variant summary

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

The NM_001282597.3(CTNNA2):​c.852+13567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,948 control chromosomes in the GnomAD database, including 3,035 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 0.19 (3035 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.852+13567G>A		intron_variant	Intron 6 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.852+13567G>A		intron_variant	Intron 6 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.852+13567G>A		intron_variant	Intron 6 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.852+13567G>A		intron_variant	Intron 10 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.852+13567G>A		intron_variant	Intron 6 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29333 AN: 151828 Hom.: 3035 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.193 AC: 29355 AN: 151948 Hom.: 3035 Cov.: 32 AF XY: 0.192 AC XY: 14241 AN XY: 74258

African (AFR) AF: 0.195 AC: 8094 AN: 41426

American (AMR) AF: 0.118 AC: 1800 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3470

East Asian (EAS) AF: 0.0563 AC: 290 AN: 5152

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2094 AN: 10530

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14911 AN: 67984

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.201 Hom.: 3625

Bravo AF: 0.183

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.65
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: rs17018086; hg19: chr2-80115035;