rs17477949

chr11-12197656-C-T

Variant summary

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

The NM_001282663.2(MICAL2):c.265-6594C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,160 control chromosomes in the GnomAD database, including 8,134 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 0.29 (8134 hom., cov: 33)
  • Exomes 𝑓: 0.31 (0 hom.)
• Consequence: MICAL2 NM_001282663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL2	NM_001282663.2	c.265-6594C>T		intron_variant		ENST00000683283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL2	ENST00000683283.1	c.265-6594C>T		intron_variant			NM_001282663.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44861 AN: 152014 Hom.: 8138 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.308 AC: 8 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 4 AN XY: 16

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.295 AC: 44858 AN: 152134 Hom.: 8134 Cov.: 33 AF XY: 0.292 AC XY: 21700 AN XY: 74380

Gnomad4 AFR AF: 0.0920

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.0580

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.323

Alfa AF: 0.385 Hom.: 11629

Bravo AF: 0.283

Asia WGS AF: 0.201 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.1
Dann	Benign	0.39

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: rs17477949; hg19: chr11-12219203;