9-98126584-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_052820.4(CORO2A):c.1411G>A(p.Val471Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CORO2A NM_052820.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.63

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025586545).
• BP6: Variant 9-98126584-C-T is Benign according to our data. Variant chr9-98126584-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2205127.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO2A	NM_052820.4	c.1411G>A	p.Val471Ile	missense_variant	11/12	ENST00000375077.5
CORO2A	NM_003389.3	c.1411G>A	p.Val471Ile	missense_variant	11/12
CORO2A	XM_011518986.4	c.1411G>A	p.Val471Ile	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO2A	ENST00000375077.5	c.1411G>A	p.Val471Ile	missense_variant	11/12	1	NM_052820.4	P1
CORO2A	ENST00000343933.9	c.1411G>A	p.Val471Ile	missense_variant	11/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000517 AC: 13 AN: 251380 Hom.: 0 AF XY: 0.0000662 AC XY: 9 AN XY: 135864

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727230

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152100 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74300

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.000189

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	1.4
Dann	Benign	0.76
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0096	N
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.026	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.036
Sift	Benign	0.58	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;B
Vest4		0.099
MutPred		0.31		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP		0.33
MPC		0.17
ClinPred		0.011	T
GERP RS		-5.1
Varity_R		0.021
gMVP		0.040

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

Other links and lift over

dbSNP: rs771489458; hg19: chr9-100888866;