rs216617

Variant names:

• chr2-80577159-G-A
• rs216617
• NM_001282597.3:c.1893+2845G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-80577159-G-A
• chr2-80577159-G-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.1893+2845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,026 control chromosomes in the GnomAD database, including 26,700 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 0.59 (26700 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 3 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

ENSG00000237031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1893+2845G>A		intron_variant	Intron 13 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1893+2845G>A		intron_variant	Intron 13 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89737 AN: 151908 Hom.: 26683 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.591 AC: 89798 AN: 152026 Hom.: 26700 Cov.: 32 AF XY: 0.589 AC XY: 43800 AN XY: 74330

African (AFR) AF: 0.515 AC: 21336 AN: 41454

American (AMR) AF: 0.623 AC: 9503 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2093 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3141 AN: 5158

South Asian (SAS) AF: 0.419 AC: 2020 AN: 4816

European-Finnish (FIN) AF: 0.645 AC: 6823 AN: 10586

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42795 AN: 67966

Other (OTH) AF: 0.631 AC: 1328 AN: 2106

Alfa AF: 0.617 Hom.: 12901

Bravo AF: 0.589

Asia WGS AF: 0.547 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		0.047
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: rs216617; hg19: chr2-80804284;