chr2-79312862-G-C

Variant names:

• chr2-79312862-G-C
• rs13409348
• NM_001399737.1:c.-318+66G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399737.1(CTNNA2):​c.-318+66G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,034 control chromosomes in the GnomAD database, including 6,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6303 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTNNA2 NM_001399737.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399737.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001399737.1		c.-318+66G>C		intron	N/A	NP_001386666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000466387.5	TSL:2	c.-318+66G>C		intron	N/A	ENSP00000418191.1
	CTNNA2	ENST00000467488.1	TSL:4	n.390+66G>C		intron	N/A
	CTNNA2	ENST00000496251.5	TSL:3	n.160+66G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41550 AN: 151916 Hom.: 6292 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.274 AC: 41598 AN: 152034 Hom.: 6303 Cov.: 33 AF XY: 0.267 AC XY: 19847 AN XY: 74344

African (AFR) AF: 0.411 AC: 17051 AN: 41466

American (AMR) AF: 0.227 AC: 3462 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3466

East Asian (EAS) AF: 0.164 AC: 846 AN: 5168

South Asian (SAS) AF: 0.197 AC: 951 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10572

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15671 AN: 67956

Other (OTH) AF: 0.285 AC: 601 AN: 2108

Alfa AF: 0.253 Hom.: 647

Bravo AF: 0.286

Asia WGS AF: 0.183 AC: 639 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.51
PhyloP100		-0.064
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: rs13409348; hg19: chr2-79539988;