2-80171581-C-T

Position:

• chr2-80171581-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282597.3(CTNNA2):​c.1057-221630C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,100 control chromosomes in the GnomAD database, including 3,839 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 0.19 (3839 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1057-221630C>T		intron_variant		ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1057-221630C>T		intron_variant		1	NM_001282597.3	ENSP00000384638
CTNNA2	ENST00000496558.5	c.1057-221630C>T		intron_variant		1		ENSP00000419295	P1
CTNNA2	ENST00000466387.5	c.1057-221630C>T		intron_variant		2		ENSP00000418191	P1
CTNNA2	ENST00000629316.2	c.1057-221630C>T		intron_variant		2		ENSP00000486160

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29123 AN: 151982 Hom.: 3827 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.192 AC: 29173 AN: 152100 Hom.: 3839 Cov.: 33 AF XY: 0.191 AC XY: 14197 AN XY: 74334

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.166

Alfa AF: 0.0886 Hom.: 178

Bravo AF: 0.202

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.085
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs17018760; hg19: chr2-80398707;