rs10520246

Variant names:

• chr2-79554543-G-T
• rs10520246
• NM_001282597.3:c.-6+41336G>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.-6+41336G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 152,188 control chromosomes in the GnomAD database, including 247 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 0.048 (247 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.-6+41336G>T		intron_variant	Intron 1 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.-6+41336G>T		intron_variant	Intron 1 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7331 AN: 152070 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0482 AC: 7332 AN: 152188 Hom.: 247 Cov.: 32 AF XY: 0.0473 AC XY: 3517 AN XY: 74402

African (AFR) AF: 0.0118 AC: 491 AN: 41556

American (AMR) AF: 0.0427 AC: 652 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00561 AC: 27 AN: 4814

European-Finnish (FIN) AF: 0.0858 AC: 909 AN: 10592

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0703 AC: 4782 AN: 67984

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0637 Hom.: 196

Bravo AF: 0.0446

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.14
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: rs10520246; hg19: chr2-79781669;