chr2-79523156-A-G

Position:

• chr2-79523156-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282597.3(CTNNA2):​c.-6+9949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 359,794 control chromosomes in the GnomAD database, including 9,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4400 hom., cov: 32)
  • Exomes 𝑓: 0.22 (5440 hom.)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.961

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-79523156-A-G is Benign according to our data. Variant chr2-79523156-A-G is described in ClinVar as [Benign]. Clinvar id is 1248104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.-6+9949A>G		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.-6+9949A>G		intron_variant		1	NM_001282597.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35321 AN: 151872 Hom.: 4397 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.216 AC: 44887 AN: 207804 Hom.: 5440 AF XY: 0.225 AC XY: 26966 AN XY: 119900

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.232 AC: 35337 AN: 151990 Hom.: 4400 Cov.: 32 AF XY: 0.231 AC XY: 17188 AN XY: 74302

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.255

Alfa AF: 0.212 Hom.: 744

Bravo AF: 0.235

Asia WGS AF: 0.187 AC: 653 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.58

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: rs72921161; hg19: chr2-79750282;