rs2974151

Variant names:

• chr2-79926171-C-G
• rs2974151
• NM_001282597.3:c.1056+16374C>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+16374C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,106 control chromosomes in the GnomAD database, including 1,946 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 0.15 (1946 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.1056+16374C>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+16374C>G		intron_variant	Intron 7 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.1056+16374C>G		intron_variant	Intron 7 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.1056+16374C>G		intron_variant	Intron 11 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.1056+16374C>G		intron_variant	Intron 7 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23125 AN: 151990 Hom.: 1943 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.152 AC: 23142 AN: 152106 Hom.: 1946 Cov.: 32 AF XY: 0.153 AC XY: 11396 AN XY: 74348

African (AFR) AF: 0.143 AC: 5933 AN: 41520

American (AMR) AF: 0.249 AC: 3797 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1320 AN: 5162

South Asian (SAS) AF: 0.158 AC: 764 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1361 AN: 10600

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9153 AN: 67970

Other (OTH) AF: 0.161 AC: 338 AN: 2102

Alfa AF: 0.147 Hom.: 232

Bravo AF: 0.167

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.75
PhyloP100		-0.31
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: rs2974151; hg19: chr2-80153297;