2-80034044-C-T

Variant names:

• chr2-80034044-C-T
• rs6729700
• NM_001282597.3:c.1056+124247C>T

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1056+124247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 147,614 control chromosomes in the GnomAD database, including 16,165 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 0.44 (16165 hom., cov: 27)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.1056+124247C>T		intron	N/A	NP_001269526.1
	CTNNA2	NM_001282598.2		c.1158+124247C>T		intron	N/A	NP_001269527.1
	CTNNA2	NM_001399737.1		c.1056+124247C>T		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.1056+124247C>T		intron	N/A	ENSP00000384638.4
	CTNNA2	ENST00000496558.5	TSL:1	c.1056+124247C>T		intron	N/A	ENSP00000419295.1
	CTNNA2	ENST00000466387.5	TSL:2	c.1056+124247C>T		intron	N/A	ENSP00000418191.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 65046 AN: 147544 Hom.: 16171 Cov.: 27

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.441 AC: 65051 AN: 147614 Hom.: 16165 Cov.: 27 AF XY: 0.446 AC XY: 32031 AN XY: 71768

African (AFR) AF: 0.220 AC: 8862 AN: 40302

American (AMR) AF: 0.583 AC: 8658 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1893 AN: 3458

East Asian (EAS) AF: 0.868 AC: 4369 AN: 5034

South Asian (SAS) AF: 0.543 AC: 2532 AN: 4660

European-Finnish (FIN) AF: 0.486 AC: 4308 AN: 8856

Middle Eastern (MID) AF: 0.468 AC: 133 AN: 284

European-Non Finnish (NFE) AF: 0.487 AC: 32753 AN: 67190

Other (OTH) AF: 0.488 AC: 1009 AN: 2066

Alfa AF: 0.490 Hom.: 33733

Bravo AF: 0.441

Asia WGS AF: 0.649 AC: 2253 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.57
PhyloP100		-0.24
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: rs6729700; hg19: chr2-80261170;