NM_001282597.3:c.585+218T>A

Variant names:

• chr2-79870153-T-A
• rs3755095
• NM_001282597.3:c.585+218T>A

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.585+218T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,946 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• 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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.585+218T>A		intron_variant	Intron 5 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.585+218T>A		intron_variant	Intron 5 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.585+218T>A		intron_variant	Intron 5 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.585+218T>A		intron_variant	Intron 9 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.585+218T>A		intron_variant	Intron 5 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 2661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		-0.38

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: rs3755095; hg19: chr2-80097279;