chr2-79523465-G-T

Variant names:

• chr2-79523465-G-T
• rs10206130
• NM_001282597.3:c.-6+10258G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001282597.3(CTNNA2):​c.-6+10258G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,994 control chromosomes in the GnomAD database, including 32,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (32906 hom., cov: 33)
• Consequence: CTNNA2 NM_001282597.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-79523465-G-T is Benign according to our data. Variant chr2-79523465-G-T is described in ClinVar as [Benign]. Clinvar id is 1249105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA2	NM_001282597.3	c.-6+10258G>T		intron_variant	Intron 1 of 18	ENST00000402739.9	NP_001269526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA2	ENST00000402739.9	c.-6+10258G>T		intron_variant	Intron 1 of 18	1	NM_001282597.3	ENSP00000384638.4

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99812 AN: 151878 Hom.: 32878 Cov.: 33

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.657 AC: 99887 AN: 151994 Hom.: 32906 Cov.: 33 AF XY: 0.655 AC XY: 48673 AN XY: 74294

African (AFR) AF: 0.642 AC: 26604 AN: 41422

American (AMR) AF: 0.572 AC: 8736 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2494 AN: 3466

East Asian (EAS) AF: 0.661 AC: 3415 AN: 5170

South Asian (SAS) AF: 0.655 AC: 3161 AN: 4828

European-Finnish (FIN) AF: 0.699 AC: 7387 AN: 10564

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45858 AN: 67964

Other (OTH) AF: 0.647 AC: 1366 AN: 2110

Alfa AF: 0.668 Hom.: 29552

Bravo AF: 0.647

Asia WGS AF: 0.654 AC: 2278 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.3
DANN	Benign	0.19
PhyloP100		1.3
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: rs10206130; hg19: chr2-79750591;