2-79744351-G-A

Position:

• chr2-79744351-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.00900

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 -14 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_single_submitter, 1 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/exons	MANE	UniProt
CTNNA2	NM_001282597.3	c.103-36G>A		intron_variant		ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9	c.103-36G>A		intron_variant		1	NM_001282597.3

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

GnomAD3 exomes AF: 0.0114 AC: 2359 AN: 207496 Hom.: 142 AF XY: 0.00822 AC XY: 927 AN XY: 112842

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 SAS exome AF: 0.0000898

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.00749

Gnomad4 ASJ exome AF: 0.000826

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000274

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.00834

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0282 Hom.: 65

Bravo AF: 0.0459

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs17017796; hg19: chr2-79971477;