9-98126578-C-G

Variant names:

• chr9-98126578-C-G
• rs773618810
• NM_052820.4:c.1417G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052820.4(CORO2A):​c.1417G>C​(p.Glu473Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E473K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CORO2A NM_052820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37267864).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO2A	NM_052820.4	MANE Select	c.1417G>C	p.Glu473Gln	missense	Exon 11 of 12	NP_438171.1	Q92828
	CORO2A	NM_003389.3		c.1417G>C	p.Glu473Gln	missense	Exon 11 of 12	NP_003380.3	A8K9S3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO2A	ENST00000375077.5	TSL:1 MANE Select	c.1417G>C	p.Glu473Gln	missense	Exon 11 of 12	ENSP00000364218.4	Q92828
	CORO2A	ENST00000343933.9	TSL:1	c.1417G>C	p.Glu473Gln	missense	Exon 11 of 12	ENSP00000343746.5	Q92828
	CORO2A	ENST00000948662.1		c.1627G>C	p.Glu543Gln	missense	Exon 12 of 13	ENSP00000618721.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.65		Loss of sheet (P = 0.0357)
MVP		0.71
MPC		0.66
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.17
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs773618810; hg19: chr9-100888860;