chr2-80534067-A-C

Variant names:

• chr2-80534067-A-C
• rs12611756
• NM_001282597.3:c.1291-10915A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282597.3(CTNNA2):​c.1291-10915A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,010 control chromosomes in the GnomAD database, including 36,844 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 0.69 (36844 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1291-10915A>C		intron_variant	Intron 9 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1291-10915A>C		intron_variant	Intron 9 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104336 AN: 151892 Hom.: 36795 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.687 AC: 104442 AN: 152010 Hom.: 36844 Cov.: 32 AF XY: 0.686 AC XY: 51006 AN XY: 74300

African (AFR) AF: 0.850 AC: 35259 AN: 41484

American (AMR) AF: 0.602 AC: 9183 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2048 AN: 5148

South Asian (SAS) AF: 0.739 AC: 3556 AN: 4814

European-Finnish (FIN) AF: 0.688 AC: 7278 AN: 10584

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43041 AN: 67960

Other (OTH) AF: 0.621 AC: 1307 AN: 2106

Alfa AF: 0.650 Hom.: 93105

Bravo AF: 0.684

Asia WGS AF: 0.609 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.69
PhyloP100		0.86
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: rs12611756; hg19: chr2-80761192;