Variant chr11-12162276-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001282663.2(MICAL2):c.121C>G(p.Leu41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,614,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

MICAL2
NM_001282663.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

MICAL2 (HGNC:24693): (microtubule associated monooxygenase, calponin and LIM domain containing 2) The protein encoded by this gene is a monooxygenase that enhances depolymerization of F-actin and is therefore involved in cytoskeletal dynamics. The encoded protein is a regulator of the SRF signaling pathway. Increased expression of this gene has been associated with cancer progression and metastasis. [provided by RefSeq, Oct 2016]

MICAL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006238103).

BP6

Variant 11-12162276-C-G is Benign according to our data. Variant chr11-12162276-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 786189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL2	NM_001282663.2 linkuse as main transcript	c.121C>G	p.Leu41Val	missense_variant	3/28	ENST00000683283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL2	ENST00000683283.1 linkuse as main transcript	c.121C>G	p.Leu41Val	missense_variant	3/28		NM_001282663.2		O94851-1

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

366

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00837

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000632

AC:

159

AN:

251450

Hom.:

AF XY:

0.000508

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00923

Gnomad AMR exome

AF:

0.000173

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000220

AC:

321

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00800

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152356

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00849

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.00269

ESP6500AA

AF:

0.00954

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000799

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;.;T;.;.;.;T;T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.0062

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;.;M;.;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;D;N;D;N;D;D;D;.

REVEL

Benign

0.10

Sift

Benign

0.10

T;T;T;T;T;T;T;T;.

Sift4G

Benign

0.072

T;T;T;T;T;T;T;T;.

Polyphen

0.89

.;.;P;.;.;.;.;.;.

Vest4

0.70, 0.69

MVP

0.71

MPC

1.4

ClinPred

0.056

GERP RS

5.5

Varity_R

0.25

gMVP

0.60

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