Variant 15-68645343-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006091.5(CORO2B):c.199G>A(p.Val67Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,611,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CORO2B
NM_006091.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

CORO2B (HGNC:2256): (coronin 2B) Enables talin binding activity and vinculin binding activity. Acts upstream of or within several processes, including negative regulation of cell-substrate adhesion; regulation of actin cytoskeleton organization; and regulation of establishment of protein localization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

CORO2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2961768).

BS2

High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO2B	NM_006091.5 linkuse as main transcript	c.199G>A	p.Val67Ile	missense_variant	2/12	ENST00000261861.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO2B	ENST00000261861.10 linkuse as main transcript	c.199G>A	p.Val67Ile	missense_variant	2/12	1	NM_006091.5	P4	Q9UQ03-1
CORO2B	ENST00000540068.6 linkuse as main transcript	c.184G>A	p.Val62Ile	missense_variant	2/12	5		A1	Q9UQ03-2
CORO2B	ENST00000543950.3 linkuse as main transcript	c.184G>A	p.Val62Ile	missense_variant	2/12	2		A1	Q9UQ03-2

Frequencies

GnomAD3 genomes

AF:

0.0000859

AC:

AN:

151414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000461

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000781

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000137

AC:

AN:

248498

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000713

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1459526

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000858

AC:

AN:

151532

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000460

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000782

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 24, 2024

The c.199G>A (p.V67I) alteration is located in exon 2 (coding exon 2) of the CORO2B gene. This alteration results from a G to A substitution at nucleotide position 199, causing the valine (V) at amino acid position 67 to be replaced by an isoleucine (I). 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

0.097

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;.;.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.86

N;N;N;N

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.28

MutPred

0.82

Gain of catalytic residue at P69 (P = 0.0332);.;.;.;

MVP

0.62

MPC

1.0

ClinPred

0.32

GERP RS

4.6

Varity_R

0.45

gMVP

0.20

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.

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