2-79891074-G-C

Variant names:

• chr2-79891074-G-C
• rs9309553
• NM_001282597.3:c.852+16732G>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.852+16732G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 151,382 control chromosomes in the GnomAD database, including 333 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 0.031 (333 hom., cov: 31)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 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.852+16732G>C		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.954+16732G>C		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.852+16732G>C		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.852+16732G>C		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.852+16732G>C		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000466387.5	TSL:2	c.852+16732G>C		intron	N/A	ENSP00000418191.1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4652 AN: 151264 Hom.: 329 Cov.: 31

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0318

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00683

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0308 AC: 4670 AN: 151382 Hom.: 333 Cov.: 31 AF XY: 0.0334 AC XY: 2466 AN XY: 73894

African (AFR) AF: 0.0338 AC: 1395 AN: 41220

American (AMR) AF: 0.0476 AC: 720 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 110 AN: 3458

East Asian (EAS) AF: 0.311 AC: 1583 AN: 5084

South Asian (SAS) AF: 0.0604 AC: 286 AN: 4736

European-Finnish (FIN) AF: 0.00143 AC: 15 AN: 10520

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00681 AC: 463 AN: 67944

Other (OTH) AF: 0.0446 AC: 93 AN: 2086

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.0370

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.44
DANN	Benign	0.65
PhyloP100		-0.83
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: rs9309553; hg19: chr2-80118200;