chr2-80054047-A-G

Variant names:

• chr2-80054047-A-G
• rs6738962
• NM_001282597.3:c.1056+144250A>G

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+144250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,326 control chromosomes in the GnomAD database, including 684 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 0.077 (684 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1056+144250A>G		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.1056+144250A>G		intron_variant	Intron 7 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.1056+144250A>G		intron_variant	Intron 7 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.1056+144250A>G		intron_variant	Intron 11 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.1056+144250A>G		intron_variant	Intron 7 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11667 AN: 152208 Hom.: 669 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0429

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0770 AC: 11733 AN: 152326 Hom.: 684 Cov.: 33 AF XY: 0.0761 AC XY: 5669 AN XY: 74472

African (AFR) AF: 0.158 AC: 6573 AN: 41566

American (AMR) AF: 0.0774 AC: 1184 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5182

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4824

European-Finnish (FIN) AF: 0.0429 AC: 456 AN: 10624

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2940 AN: 68038

Other (OTH) AF: 0.0799 AC: 169 AN: 2116

Alfa AF: 0.0581 Hom.: 869

Bravo AF: 0.0852

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.48
PhyloP100		0.55
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: rs6738962; hg19: chr2-80281173;