Variant chr9-98126555-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052820.4(CORO2A):c.1440G>C(p.Glu480Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CORO2A
NM_052820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.762

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23088023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO2A	NM_052820.4 linkuse as main transcript	c.1440G>C	p.Glu480Asp	missense_variant	11/12	ENST00000375077.5	NP_438171.1	Q92828A0A024R150A8K9S3
CORO2A	NM_003389.3 linkuse as main transcript	c.1440G>C	p.Glu480Asp	missense_variant	11/12		NP_003380.3	Q92828A0A024R150A8K9S3
CORO2A	XM_011518986.4 linkuse as main transcript	c.1440G>C	p.Glu480Asp	missense_variant	11/12		XP_011517288.1	Q92828A0A024R150

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORO2A	ENST00000375077.5 linkuse as main transcript	c.1440G>C	p.Glu480Asp	missense_variant	11/12	1	NM_052820.4	ENSP00000364218.4		Q92828
CORO2A	ENST00000343933.9 linkuse as main transcript	c.1440G>C	p.Glu480Asp	missense_variant	11/12	1		ENSP00000343746.5		Q92828

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250824

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 04, 2024

The c.1440G>C (p.E480D) alteration is located in exon 11 (coding exon 10) of the CORO2A gene. This alteration results from a G to C substitution at nucleotide position 1440, causing the glutamic acid (E) at amino acid position 480 to be replaced by an aspartic acid (D). 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

0.32

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.077

T;T

Sift4G

Uncertain

0.024

D;D

Polyphen

0.11

B;B

Vest4

0.47

MutPred

0.44

Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);

MVP

0.48

MPC

0.56

ClinPred

0.22

GERP RS

1.9

Varity_R

0.069

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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