chr2-79476375-T-C

Position:

• chr2-79476375-T-C

Variant summary

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

The NM_001399737.1(CTNNA2):​c.-134-28679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,048 control chromosomes in the GnomAD database, including 26,273 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 0.58 (26273 hom., cov: 32)
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001399737.1	c.-134-28679T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-134-28679T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87831 AN: 151930 Hom.: 26266 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.578 AC: 87876 AN: 152048 Hom.: 26273 Cov.: 32 AF XY: 0.575 AC XY: 42709 AN XY: 74322

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.592

Alfa AF: 0.620 Hom.: 3666

Bravo AF: 0.577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.89
DANN	Benign	0.68

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: rs12620205; hg19: chr2-79703501;