rs1609930

chr11-12231877-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.1996-4300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,072 control chromosomes in the GnomAD database, including 5,356 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 0.24 (5356 hom., cov: 33)
• Consequence: MICAL2 NM_001282663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL2	NM_001282663.2	c.1996-4300C>T		intron_variant		ENST00000683283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL2	ENST00000683283.1	c.1996-4300C>T		intron_variant			NM_001282663.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36871 AN: 151954 Hom.: 5353 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.243 AC: 36906 AN: 152072 Hom.: 5356 Cov.: 33 AF XY: 0.245 AC XY: 18191 AN XY: 74356

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.185

Alfa AF: 0.173 Hom.: 3410

Bravo AF: 0.239

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.66
Dann	Benign	0.53

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: rs1609930; hg19: chr11-12253424;