11-12275234-T-G

Position:

• chr11-12275234-T-G

Variant summary

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

The NM_001393937.1(MICAL2):​c.3335-752T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,966 control chromosomes in the GnomAD database, including 17,218 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 0.46 (17218 hom., cov: 32)
• Consequence: MICAL2 NM_001393937.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICAL2	NM_001393937.1	c.3335-752T>G		intron_variant			NP_001380866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICAL2	ENST00000646065.1	c.3335-752T>G		intron_variant				ENSP00000494982	P1
MICAL2	ENST00000644505.1	n.382+539T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70427 AN: 151848 Hom.: 17204 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.464 AC: 70466 AN: 151966 Hom.: 17218 Cov.: 32 AF XY: 0.471 AC XY: 35022 AN XY: 74286

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.472

Alfa AF: 0.414 Hom.: 17889

Bravo AF: 0.479

Asia WGS AF: 0.658 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7106205; hg19: chr11-12296781;