chr11-12162186-C-A

Variant names:

• chr11-12162186-C-A
• NM_001282663.2:c.31C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282663.2(MICAL2):​c.31C>A​(p.Gln11Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MICAL2 NM_001282663.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20677274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICAL2	NM_001282663.2	c.31C>A	p.Gln11Lys	missense_variant	Exon 3 of 28	ENST00000683283.1	NP_001269592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL2	ENST00000683283.1	c.31C>A	p.Gln11Lys	missense_variant	Exon 3 of 28		NM_001282663.2	ENSP00000507067.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31C>A (p.Q11K) alteration is located in exon 3 (coding exon 1) of the MICAL2 gene. This alteration results from a C to A substitution at nucleotide position 31, causing the glutamine (Q) at amino acid position 11 to be replaced by a lysine (K). 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	0.084
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T;.;T;.;.;.;T;T;.
Eigen	Benign	0.071
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;.;L;.;L;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;.
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T;T;T;T;T;T;.
Sift4G	Benign	0.52	T;T;T;T;T;T;T;T;.
Polyphen		0.23	.;.;B;.;.;.;.;.;.
Vest4		0.49, 0.52
MutPred		0.27		Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);Gain of ubiquitination at Q11 (P = 0.006);
MVP		0.63
MPC		0.87
ClinPred		0.75	D
GERP RS		5.5
PromoterAI		0.0094	Neutral
Varity_R		0.20
gMVP		0.48
Mutation Taster		=82/18	polymorphism

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-12183733;