Variant 2-79744515-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001282597.3(CTNNA2):c.231G>C(p.Gln77His) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CTNNA2
NM_001282597.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CTNNA2. . Gene score misZ 3.6298 (greater than the threshold 3.09). Trascript score misZ 3.6837 (greater than threshold 3.09). GenCC has associacion of gene with cortical dysplasia, complex, with other brain malformations 9.

BP4

Computational evidence support a benign effect (MetaRNN=0.18369594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA2	NM_001282597.3 linkuse as main transcript	c.231G>C	p.Gln77His	missense_variant	3/19	ENST00000402739.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA2	ENST00000402739.9 linkuse as main transcript	c.231G>C	p.Gln77His	missense_variant	3/19	1	NM_001282597.3		P26232-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249286

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000661

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.231G>C (p.Q77H) alteration is located in exon 3 (coding exon 2) of the CTNNA2 gene. This alteration results from a G to C substitution at nucleotide position 231, causing the glutamine (Q) at amino acid position 77 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;.;.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.9

N;N;.;D;N

REVEL

Benign

0.16

Sift

Uncertain

0.029

D;D;.;D;D

Sift4G

Uncertain

0.051

T;T;D;D;T

Polyphen

0.84

P;P;P;.;P

Vest4

0.58

MutPred

0.39

Loss of ubiquitination at K74 (P = 0.1172);Loss of ubiquitination at K74 (P = 0.1172);Loss of ubiquitination at K74 (P = 0.1172);Loss of ubiquitination at K74 (P = 0.1172);Loss of ubiquitination at K74 (P = 0.1172);

MVP

0.57

MPC

1.1

ClinPred

0.31

GERP RS

2.7

Varity_R

0.23

gMVP

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over