rs13395022

Variant names:

• chr2-79655134-T-C
• rs13395022
• NM_001282597.3:c.102+3476T>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.102+3476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,086 control chromosomes in the GnomAD database, including 4,335 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 0.23 (4335 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.102+3476T>C		intron	N/A	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.204+3476T>C		intron	N/A	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.102+3476T>C		intron	N/A	NP_001386666.1	P26232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.102+3476T>C		intron	N/A	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.102+3476T>C		intron	N/A	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000466387.5	TSL:2	c.102+3476T>C		intron	N/A	ENSP00000418191.1	P26232-2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35081 AN: 151968 Hom.: 4324 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.231 AC: 35110 AN: 152086 Hom.: 4335 Cov.: 32 AF XY: 0.233 AC XY: 17319 AN XY: 74350

African (AFR) AF: 0.285 AC: 11839 AN: 41474

American (AMR) AF: 0.182 AC: 2781 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2342 AN: 5162

South Asian (SAS) AF: 0.340 AC: 1641 AN: 4826

European-Finnish (FIN) AF: 0.191 AC: 2023 AN: 10592

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12829 AN: 67976

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.209 Hom.: 14820

Bravo AF: 0.235

Asia WGS AF: 0.364 AC: 1266 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.42
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13395022; hg19: chr2-79882260;