11-12204256-A-T

Position:

• chr11-12204256-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282663.2(MICAL2):​c.271A>T​(p.Ile91Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MICAL2 NM_001282663.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL2	NM_001282663.2	c.271A>T	p.Ile91Leu	missense_variant	4/28	ENST00000683283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL2	ENST00000683283.1	c.271A>T	p.Ile91Leu	missense_variant	4/28		NM_001282663.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.271A>T (p.I91L) alteration is located in exon 4 (coding exon 2) of the MICAL2 gene. This alteration results from a A to T substitution at nucleotide position 271, causing the isoleucine (I) at amino acid position 91 to be replaced by a leucine (L). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.;.;T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.6	.;M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D;D;D;D;D;D;.
Sift4G	Uncertain	0.013	D;D;D;D;D;D;.
Polyphen		0.78	.;P;.;.;.;.;.
Vest4		0.54, 0.55
MutPred		0.29		Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);Gain of catalytic residue at I91 (P = 0.0488);
MVP		0.82
MPC		0.82
ClinPred		0.94	D
GERP RS		1.7
Varity_R		0.25
gMVP		0.91

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: rs774020963; hg19: chr11-12225803;