2-79460126-A-C

Position:

• chr2-79460126-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399737.1(CTNNA2):​c.-134-44928A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,894 control chromosomes in the GnomAD database, including 9,363 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 0.35 (9363 hom., cov: 32)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001399737.1	c.-134-44928A>C		intron_variant			NP_001386666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-134-44928A>C		intron_variant		2		ENSP00000418191	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52968 AN: 151778 Hom.: 9355 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.349 AC: 53007 AN: 151894 Hom.: 9363 Cov.: 32 AF XY: 0.351 AC XY: 26080 AN XY: 74266

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.357

Alfa AF: 0.333 Hom.: 10012

Bravo AF: 0.348

Asia WGS AF: 0.471 AC: 1632 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs399885; hg19: chr2-79687252;