9-98126578-C-T

Position:

chr9-98126578-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052820.4(CORO2A):c.1417G>A(p.Glu473Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CORO2A
NM_052820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40120548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO2A	NM_052820.4 linkuse as main transcript	c.1417G>A	p.Glu473Lys	missense_variant	11/12	ENST00000375077.5	NP_438171.1	Q92828A0A024R150A8K9S3
CORO2A	NM_003389.3 linkuse as main transcript	c.1417G>A	p.Glu473Lys	missense_variant	11/12		NP_003380.3	Q92828A0A024R150A8K9S3
CORO2A	XM_011518986.4 linkuse as main transcript	c.1417G>A	p.Glu473Lys	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.1417G>A	p.Glu473Lys	missense_variant	11/12	1	NM_052820.4	ENSP00000364218.4		Q92828
CORO2A	ENST00000343933.9 linkuse as main transcript	c.1417G>A	p.Glu473Lys	missense_variant	11/12	1		ENSP00000343746.5		Q92828

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251296

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

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

Jul 09, 2024

The c.1417G>A (p.E473K) alteration is located in exon 11 (coding exon 10) of the CORO2A gene. This alteration results from a G to A substitution at nucleotide position 1417, causing the glutamic acid (E) at amino acid position 473 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.53

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

0.99

D;D

Vest4

0.43

MutPred

0.61

Gain of methylation at E473 (P = 1e-04);Gain of methylation at E473 (P = 1e-04);

MVP

0.80

MPC

0.51

ClinPred

0.74

GERP RS

4.3

Varity_R

0.23

gMVP

0.24

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