9-98128618-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_052820.4(CORO2A):​c.1069G>A​(p.Val357Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CORO2A
NM_052820.4 missense

Scores

10
5
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CORO2ANM_052820.4 linkc.1069G>A p.Val357Met missense_variant Exon 9 of 12 ENST00000375077.5 NP_438171.1 Q92828A0A024R150A8K9S3
CORO2ANM_003389.3 linkc.1069G>A p.Val357Met missense_variant Exon 9 of 12 NP_003380.3 Q92828A0A024R150A8K9S3
CORO2AXM_011518986.4 linkc.1069G>A p.Val357Met missense_variant Exon 9 of 12 XP_011517288.1 Q92828A0A024R150

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CORO2AENST00000375077.5 linkc.1069G>A p.Val357Met missense_variant Exon 9 of 12 1 NM_052820.4 ENSP00000364218.4 Q92828
CORO2AENST00000343933.9 linkc.1069G>A p.Val357Met missense_variant Exon 9 of 12 1 ENSP00000343746.5 Q92828

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251454
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000137
AC:
2
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1069G>A (p.V357M) alteration is located in exon 9 (coding exon 8) of the CORO2A gene. This alteration results from a G to A substitution at nucleotide position 1069, causing the valine (V) at amino acid position 357 to be replaced by a methionine (M). 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
Pathogenic
0.91
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;D
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
.;D
M_CAP
Benign
0.083
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Pathogenic
3.3
M;M
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.93
MutPred
0.94
Gain of disorder (P = 0.0344);Gain of disorder (P = 0.0344);
MVP
0.73
MPC
0.81
ClinPred
0.98
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.67
gMVP
0.78

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.

Other links and lift over

dbSNP: rs757796002; hg19: chr9-100890900; API