2-79651538-A-G

Variant names:

• chr2-79651538-A-G
• rs3739139
• NM_001282597.3:c.-5-14A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282597.3(CTNNA2):​c.-5-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,600,996 control chromosomes in the GnomAD database, including 35,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6730 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29003 hom.)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.47
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-79651538-A-G is Benign according to our data. Variant chr2-79651538-A-G is described in ClinVar as [Benign]. Clinvar id is 1255414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.-5-14A>G		intron_variant	Intron 1 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.-5-14A>G		intron_variant	Intron 1 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40080 AN: 151930 Hom.: 6696 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.219 AC: 54537 AN: 248690 AF XY: 0.215

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.188 AC: 273051 AN: 1448948 Hom.: 29003 Cov.: 29 AF XY: 0.189 AC XY: 136591 AN XY: 721668

African (AFR) AF: 0.492 AC: 16320 AN: 33164

American (AMR) AF: 0.248 AC: 11047 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5378 AN: 26014

East Asian (EAS) AF: 0.319 AC: 12652 AN: 39624

South Asian (SAS) AF: 0.269 AC: 23135 AN: 85950

European-Finnish (FIN) AF: 0.132 AC: 7024 AN: 53362

Middle Eastern (MID) AF: 0.167 AC: 960 AN: 5738

European-Non Finnish (NFE) AF: 0.167 AC: 184046 AN: 1100572

Other (OTH) AF: 0.208 AC: 12489 AN: 59924

GnomAD4 genome AF: 0.264 AC: 40167 AN: 152048 Hom.: 6730 Cov.: 32 AF XY: 0.264 AC XY: 19622 AN XY: 74326

African (AFR) AF: 0.472 AC: 19537 AN: 41432

American (AMR) AF: 0.251 AC: 3839 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1513 AN: 5152

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10604

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11164 AN: 67982

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.187 Hom.: 2412

Bravo AF: 0.280

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cortical dysplasia, complex, with other brain malformations 9 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0040
DANN	Benign	0.45
PhyloP100		-1.5
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: rs3739139; hg19: chr2-79878664; COSMIC: COSV63554420; COSMIC: COSV63554420;