2-80171581-C-T

Variant names:

• chr2-80171581-C-T
• rs17018760
• NM_001282597.3:c.1057-221630C>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.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
• Publications: 3 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1057-221630C>T		intron_variant	Intron 7 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.1057-221630C>T		intron_variant	Intron 7 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.1057-221630C>T		intron_variant	Intron 7 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.1057-221630C>T		intron_variant	Intron 11 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.1057-221630C>T		intron_variant	Intron 7 of 16	2		ENSP00000486160.1

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

African (AFR) AF: 0.368 AC: 15266 AN: 41464

American (AMR) AF: 0.178 AC: 2727 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.122 AC: 633 AN: 5170

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4818

European-Finnish (FIN) AF: 0.0750 AC: 794 AN: 10582

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7537 AN: 68002

Other (OTH) AF: 0.166 AC: 350 AN: 2106

Alfa AF: 0.0974 Hom.: 229

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
PhyloP100		-2.0
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: rs17018760; hg19: chr2-80398707;