2-80622686-C-T

Variant names:

• chr2-80622686-C-T
• rs3770369
• NM_001282597.3:c.2574+3458C>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.2574+3458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,582 control chromosomes in the GnomAD database, including 23,397 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 0.55 (23397 hom., cov: 31)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.2574+3458C>T		intron_variant	Intron 18 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.2574+3458C>T		intron_variant	Intron 18 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83325 AN: 151464 Hom.: 23364 Cov.: 31

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.550 AC: 83410 AN: 151582 Hom.: 23397 Cov.: 31 AF XY: 0.549 AC XY: 40648 AN XY: 74010

African (AFR) AF: 0.654 AC: 27066 AN: 41374

American (AMR) AF: 0.565 AC: 8574 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3223 AN: 5102

South Asian (SAS) AF: 0.381 AC: 1836 AN: 4816

European-Finnish (FIN) AF: 0.480 AC: 5045 AN: 10516

Middle Eastern (MID) AF: 0.603 AC: 175 AN: 290

European-Non Finnish (NFE) AF: 0.503 AC: 34091 AN: 67836

Other (OTH) AF: 0.567 AC: 1191 AN: 2102

Alfa AF: 0.521 Hom.: 80163

Bravo AF: 0.566

Asia WGS AF: 0.521 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.050
DANN	Benign	0.64
PhyloP100		-2.0
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: rs3770369; hg19: chr2-80849811;