2-79873914-A-G

Position:

• chr2-79873914-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.586-162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,170 control chromosomes in the GnomAD database, including 666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.062 (666 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.80

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=-0.87).
• BP6: Variant 2-79873914-A-G is Benign according to our data. Variant chr2-79873914-A-G is described in ClinVar as [Benign]. Clinvar id is 1247571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.586-162A>G		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.586-162A>G		intron_variant		1	NM_001282597.3
CTNNA2	ENST00000496558.5	c.586-162A>G		intron_variant		1		P1
CTNNA2	ENST00000466387.5	c.586-162A>G		intron_variant		2		P1
CTNNA2	ENST00000629316.2	c.586-162A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9350 AN: 152054 Hom.: 663 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0286

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00899

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0615 AC: 9360 AN: 152170 Hom.: 666 Cov.: 32 AF XY: 0.0652 AC XY: 4851 AN XY: 74400

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0286

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.00897

Gnomad4 OTH AF: 0.0721

Alfa AF: 0.0354 Hom.: 39

Bravo AF: 0.0789

Asia WGS AF: 0.161 AC: 561 AN: 3478

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.55

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: rs72918621; hg19: chr2-80101040;