chr2-80488024-T-G

Variant names:

• chr2-80488024-T-G
• rs7600563
• NM_001282597.3:c.1291-56958T>G

Variant summary

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

The NM_001282597.3(CTNNA2):​c.1291-56958T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,092 control chromosomes in the GnomAD database, including 9,316 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 0.34 (9316 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282597.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	NM_001282597.3	MANE Select	c.1291-56958T>G		intron	N/A	NP_001269526.1	P26232-1
	CTNNA2	NM_001282598.2		c.1393-56958T>G		intron	N/A	NP_001269527.1	P26232-5
	CTNNA2	NM_001399737.1		c.1291-56958T>G		intron	N/A	NP_001386666.1	P26232-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA2	ENST00000402739.9	TSL:1 MANE Select	c.1291-56958T>G		intron	N/A	ENSP00000384638.4	P26232-1
	CTNNA2	ENST00000496558.5	TSL:1	c.1291-56958T>G		intron	N/A	ENSP00000419295.1	P26232-2
	CTNNA2	ENST00000343114.7	TSL:1	c.328-56958T>G		intron	N/A	ENSP00000341500.3	P26232-6

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52033 AN: 151974 Hom.: 9307 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.342 AC: 52076 AN: 152092 Hom.: 9316 Cov.: 32 AF XY: 0.347 AC XY: 25783 AN XY: 74352

African (AFR) AF: 0.333 AC: 13803 AN: 41492

American (AMR) AF: 0.400 AC: 6111 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3196 AN: 5154

South Asian (SAS) AF: 0.512 AC: 2467 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10582

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21253 AN: 67974

Other (OTH) AF: 0.379 AC: 802 AN: 2114

Alfa AF: 0.317 Hom.: 6666

Bravo AF: 0.353

Asia WGS AF: 0.532 AC: 1844 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.77
PhyloP100		-0.31
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: rs7600563; hg19: chr2-80715149;