chr2-79385309-T-C

Variant names:

• chr2-79385309-T-C
• rs11126722
• NM_001399737.1:c.-135+11296T>C

Variant summary

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

The NM_001399737.1(CTNNA2):​c.-135+11296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,948 control chromosomes in the GnomAD database, including 16,193 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 0.44 (16193 hom., cov: 32)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• 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 (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001399737.1	c.-135+11296T>C		intron_variant	Intron 4 of 21		NP_001386666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-135+11296T>C		intron_variant	Intron 4 of 21	2		ENSP00000418191.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66307 AN: 151830 Hom.: 16165 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.437 AC: 66380 AN: 151948 Hom.: 16193 Cov.: 32 AF XY: 0.443 AC XY: 32880 AN XY: 74266

African (AFR) AF: 0.660 AC: 27360 AN: 41428

American (AMR) AF: 0.413 AC: 6304 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2543 AN: 5120

South Asian (SAS) AF: 0.424 AC: 2042 AN: 4812

European-Finnish (FIN) AF: 0.453 AC: 4787 AN: 10568

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21048 AN: 67970

Other (OTH) AF: 0.426 AC: 901 AN: 2114

Alfa AF: 0.421 Hom.: 2205

Bravo AF: 0.446

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.93
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: rs11126722; hg19: chr2-79612435;