2-80311294-A-C

Variant names:

• chr2-80311294-A-C
• rs1446109
• NM_001282597.3:c.1057-81917A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282597.3(CTNNA2):​c.1057-81917A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.1057-81917A>C		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.1159-81917A>C		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.1057-81917A>C		intron	N/A	NP_001386666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.1057-81917A>C		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.1057-81917A>C		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000541047.5	TSL:1	c.-49+5971A>C		intron	N/A	ENSP00000444675.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.24

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: rs1446109; hg19: chr2-80538419;