2-79744351-G-A

Variant names:

• chr2-79744351-G-A
• rs17017796
• NM_001282597.3:c.103-36G>A

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.103-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,552,530 control chromosomes in the GnomAD database, including 705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (356 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (349 hom.)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00900
• Publications: 1 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=-0.85).
• BP6: Variant 2-79744351-G-A is Benign according to our data. Variant chr2-79744351-G-A is described in ClinVar as [Benign]. Clinvar id is 1222474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.103-36G>A		intron_variant	Intron 2 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.103-36G>A		intron_variant	Intron 2 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5988 AN: 152060 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0114 AC: 2359 AN: 207496 AF XY: 0.00822

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.00633

Gnomad ASJ exome AF: 0.000584

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000451

Gnomad OTH exome AF: 0.00583

GnomAD4 exome AF: 0.00396 AC: 5545 AN: 1400352 Hom.: 349 Cov.: 28 AF XY: 0.00346 AC XY: 2401 AN XY: 693406

African (AFR) AF: 0.145 AC: 4472 AN: 30758

American (AMR) AF: 0.00749 AC: 249 AN: 33224

Ashkenazi Jewish (ASJ) AF: 0.000826 AC: 19 AN: 22990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39118

South Asian (SAS) AF: 0.000274 AC: 21 AN: 76748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51682

Middle Eastern (MID) AF: 0.00763 AC: 40 AN: 5240

European-Non Finnish (NFE) AF: 0.000243 AC: 263 AN: 1082928

Other (OTH) AF: 0.00834 AC: 481 AN: 57664

GnomAD4 genome AF: 0.0394 AC: 6003 AN: 152178 Hom.: 356 Cov.: 32 AF XY: 0.0376 AC XY: 2800 AN XY: 74402

African (AFR) AF: 0.137 AC: 5700 AN: 41488

American (AMR) AF: 0.0129 AC: 198 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68016

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0258 Hom.: 96

Bravo AF: 0.0459

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 20, 2021

GeneDx

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	-0.85
CADD	Benign	4.4
DANN	Benign	0.56
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17017796; hg19: chr2-79971477;