Variant 9-98134844-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052820.4(CORO2A):c.430G>A(p.Ala144Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000237 in 1,613,814 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

CORO2A
NM_052820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

CORO2A (HGNC:2255): (coronin 2A) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 5 WD repeats, and has a structural similarity with actin-binding proteins: the D. discoideum coronin and the human p57 protein, suggesting that this protein may also be an actin-binding protein that regulates cell motility. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

CORO2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010443747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CORO2A	NM_052820.4 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	4/12	ENST00000375077.5
CORO2A	NM_003389.3 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	4/12
CORO2A	XM_011518986.4 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO2A	ENST00000375077.5 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	4/12	1	NM_052820.4	P1
CORO2A	ENST00000343933.9 linkuse as main transcript	c.430G>A	p.Ala144Thr	missense_variant	4/12	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000416

AC:

104

AN:

249902

Hom.:

AF XY:

0.000385

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00837

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000227

AC:

332

AN:

1461598

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00926

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000328

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.430G>A (p.A144T) alteration is located in exon 4 (coding exon 3) of the CORO2A gene. This alteration results from a G to A substitution at nucleotide position 430, causing the alanine (A) at amino acid position 144 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.42

T;T

Eigen

Benign

-0.044

Eigen_PC

Benign

0.0016

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.023

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.25

Sift

Benign

0.16

T;T

Sift4G

Benign

0.082

T;T

Polyphen

0.13

B;B

Vest4

0.38

MVP

0.78

MPC

0.40

ClinPred

0.12

GERP RS

4.6

Varity_R

0.10

gMVP

0.61

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