2-79870153-T-C

Variant names:

• chr2-79870153-T-C
• rs3755095
• NM_001282597.3:c.585+218T>C

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.585+218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,020 control chromosomes in the GnomAD database, including 6,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.24 (6341 hom., cov: 32)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.380
• 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=-1.0).
• BP6: Variant 2-79870153-T-C is Benign according to our data. Variant chr2-79870153-T-C is described in ClinVar as [Benign]. Clinvar id is 1274812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.585+218T>C		intron_variant	Intron 5 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.585+218T>C		intron_variant	Intron 5 of 18	1	NM_001282597.3	ENSP00000384638.4
CTNNA2	ENST00000496558.5	c.585+218T>C		intron_variant	Intron 5 of 17	1		ENSP00000419295.1
CTNNA2	ENST00000466387.5	c.585+218T>C		intron_variant	Intron 9 of 21	2		ENSP00000418191.1
CTNNA2	ENST00000629316.2	c.585+218T>C		intron_variant	Intron 5 of 16	2		ENSP00000486160.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35663 AN: 151902 Hom.: 6305 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.235 AC: 35748 AN: 152020 Hom.: 6341 Cov.: 32 AF XY: 0.245 AC XY: 18172 AN XY: 74308

African (AFR) AF: 0.394 AC: 16309 AN: 41426

American (AMR) AF: 0.379 AC: 5799 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.654 AC: 3363 AN: 5142

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4820

European-Finnish (FIN) AF: 0.168 AC: 1777 AN: 10590

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6019 AN: 67976

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.121 Hom.: 2661

Bravo AF: 0.264

Asia WGS AF: 0.458 AC: 1592 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 11, 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	-1.0
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-0.38
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: rs3755095; hg19: chr2-80097279;