NM_001282597.3:c.299-35421C>T

Variant names:

• chr2-79822592-C-T
• rs4852531
• NM_001282597.3:c.299-35421C>T

Variant summary

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

The NM_001282597.3(CTNNA2):​c.299-35421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,836 control chromosomes in the GnomAD database, including 17,578 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 0.47 (17578 hom., cov: 30)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 9 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 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.299-35421C>T		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.401-35421C>T		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.299-35421C>T		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.299-35421C>T		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.299-35421C>T		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000466387.5	TSL:2	c.299-35421C>T		intron	N/A	ENSP00000418191.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71223 AN: 151716 Hom.: 17559 Cov.: 30

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.469 AC: 71272 AN: 151836 Hom.: 17578 Cov.: 30 AF XY: 0.469 AC XY: 34802 AN XY: 74216

African (AFR) AF: 0.298 AC: 12312 AN: 41380

American (AMR) AF: 0.515 AC: 7857 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2056 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2975 AN: 5140

South Asian (SAS) AF: 0.515 AC: 2474 AN: 4808

European-Finnish (FIN) AF: 0.467 AC: 4922 AN: 10540

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36949 AN: 67942

Other (OTH) AF: 0.500 AC: 1055 AN: 2112

Alfa AF: 0.521 Hom.: 44226

Bravo AF: 0.466

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.47
PhyloP100		-3.3
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: rs4852531; hg19: chr2-80049718;