chr2-79673969-A-G

Variant names:

• chr2-79673969-A-G
• rs11126740
• NM_001282597.3:c.102+22311A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282597.3(CTNNA2):​c.102+22311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,020 control chromosomes in the GnomAD database, including 30,440 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 0.63 (30440 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 12 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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 (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282597.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.102+22311A>G		intron	N/A	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.204+22311A>G		intron	N/A	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.102+22311A>G		intron	N/A	NP_001386666.1	P26232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.102+22311A>G		intron	N/A	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.102+22311A>G		intron	N/A	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000466387.5	TSL:2	c.102+22311A>G		intron	N/A	ENSP00000418191.1	P26232-2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95253 AN: 151902 Hom.: 30414 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.627 AC: 95323 AN: 152020 Hom.: 30440 Cov.: 33 AF XY: 0.632 AC XY: 46965 AN XY: 74310

African (AFR) AF: 0.526 AC: 21814 AN: 41440

American (AMR) AF: 0.701 AC: 10700 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2626 AN: 3472

East Asian (EAS) AF: 0.918 AC: 4749 AN: 5176

South Asian (SAS) AF: 0.758 AC: 3651 AN: 4818

European-Finnish (FIN) AF: 0.579 AC: 6113 AN: 10552

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43348 AN: 67974

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.640 Hom.: 74771

Bravo AF: 0.631

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		0.0060
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: rs11126740; hg19: chr2-79901095;