rs11022270

chr11-12270778-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393937.1(MICAL2):c.3335-5208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,044 control chromosomes in the GnomAD database, including 27,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27868 hom., cov: 33)
• Consequence: MICAL2 NM_001393937.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL2	NM_001393937.1	c.3335-5208T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL2	ENST00000646065.1	c.3335-5208T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90935 AN: 151926 Hom.: 27836 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 91013 AN: 152044 Hom.: 27868 Cov.: 33 AF XY: 0.595 AC XY: 44237 AN XY: 74318

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.607

Alfa AF: 0.606 Hom.: 6020

Bravo AF: 0.588

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.53
Dann	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11022270; hg19: chr11-12292325;