2-80546005-A-C

Variant names:

• chr2-80546005-A-C
• NM_001282597.3:c.1482A>C
• CTNNA2 p.Arg494Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001282597.3(CTNNA2):​c.1482A>C​(p.Arg494Arg) variant causes a synonymous 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.257 with no splicing effect.

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.1482A>C	p.Arg494Arg	synonymous	Exon 11 of 19	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.1584A>C	p.Arg528Arg	synonymous	Exon 11 of 18	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.1482A>C	p.Arg494Arg	synonymous	Exon 15 of 22	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.1482A>C	p.Arg494Arg	synonymous	Exon 11 of 19	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.1482A>C	p.Arg494Arg	synonymous	Exon 11 of 18	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000343114.7	TSL:1	c.519A>C	p.Arg173Arg	synonymous	Exon 5 of 12	ENSP00000341500.3	P26232-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.64
PhyloP100		-0.26
Mutation Taster		=91/9	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-80773130;