rs13409348

chr2-79312862-G-C

Variant summary

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

The NM_001399737.1(CTNNA2):c.-318+66G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,034 control chromosomes in the GnomAD database, including 6,303 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 0.27 (6303 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001399737.1	c.-318+66G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000466387.5	c.-318+66G>C		intron_variant		2		P1
CTNNA2	ENST00000467488.1	n.390+66G>C		intron_variant, non_coding_transcript_variant		4
CTNNA2	ENST00000496251.5	n.160+66G>C		intron_variant, non_coding_transcript_variant		3
CTNNA2	ENST00000497804.1	n.87+66G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41550 AN: 151916 Hom.: 6292 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.274 AC: 41598 AN: 152034 Hom.: 6303 Cov.: 33 AF XY: 0.267 AC XY: 19847 AN XY: 74344

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.285

Alfa AF: 0.253 Hom.: 647

Bravo AF: 0.286

Asia WGS AF: 0.183 AC: 639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.51

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: rs13409348; hg19: chr2-79539988;