rs11883960

Variant names:

• chr2-80049969-C-T
• rs11883960
• NM_001282597.3:c.1056+140172C>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.1056+140172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,120 control chromosomes in the GnomAD database, including 1,555 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 0.11 (1555 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1056+140172C>T		intron_variant	Intron 7 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1056+140172C>T		intron_variant	Intron 7 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.1056+140172C>T		intron_variant	Intron 7 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.1056+140172C>T		intron_variant	Intron 11 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.1056+140172C>T		intron_variant	Intron 7 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15998 AN: 152002 Hom.: 1547 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.106 AC: 16058 AN: 152120 Hom.: 1555 Cov.: 32 AF XY: 0.104 AC XY: 7751 AN XY: 74386

African (AFR) AF: 0.259 AC: 10729 AN: 41452

American (AMR) AF: 0.0862 AC: 1318 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5168

South Asian (SAS) AF: 0.0297 AC: 143 AN: 4822

European-Finnish (FIN) AF: 0.0426 AC: 452 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2937 AN: 68002

Other (OTH) AF: 0.103 AC: 217 AN: 2104

Alfa AF: 0.0690 Hom.: 360

Bravo AF: 0.117

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.53
PhyloP100		-0.060
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: rs11883960; hg19: chr2-80277095;