2-80450185-T-C

Variant names:

• chr2-80450185-T-C
• rs7609261
• NM_001282597.3:c.1290+30584T>C

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1290+30584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,018 control chromosomes in the GnomAD database, including 18,168 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 0.45 (18168 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 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.1290+30584T>C		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.1392+30584T>C		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.1290+30584T>C		intron	N/A	NP_001386666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.1290+30584T>C		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.1290+30584T>C		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000343114.7	TSL:1	c.327+30584T>C		intron	N/A	ENSP00000341500.3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68711 AN: 151902 Hom.: 18112 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.453 AC: 68833 AN: 152018 Hom.: 18168 Cov.: 33 AF XY: 0.459 AC XY: 34099 AN XY: 74288

African (AFR) AF: 0.694 AC: 28781 AN: 41460

American (AMR) AF: 0.491 AC: 7492 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1401 AN: 3462

East Asian (EAS) AF: 0.751 AC: 3873 AN: 5158

South Asian (SAS) AF: 0.537 AC: 2585 AN: 4814

European-Finnish (FIN) AF: 0.338 AC: 3578 AN: 10584

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19845 AN: 67954

Other (OTH) AF: 0.428 AC: 905 AN: 2114

Alfa AF: 0.216 Hom.: 504

Bravo AF: 0.479

Asia WGS AF: 0.647 AC: 2240 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.59
PhyloP100		-1.7
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: rs7609261; hg19: chr2-80677310;