rs17477949

Variant names:

• chr11-12197656-C-T
• rs17477949
• NM_001282663.2:c.265-6594C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MICAL2	NM_001282663.2	c.265-6594C>T		intron_variant	Intron 3 of 27	ENST00000683283.1	NP_001269592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL2	ENST00000683283.1	c.265-6594C>T		intron_variant	Intron 3 of 27		NM_001282663.2	ENSP00000507067.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 2 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 6 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0920 AC: 3819 AN: 41524

American (AMR) AF: 0.329 AC: 5033 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1507 AN: 3470

East Asian (EAS) AF: 0.0580 AC: 300 AN: 5168

South Asian (SAS) AF: 0.363 AC: 1751 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3432 AN: 10578

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27817 AN: 67972

Other (OTH) AF: 0.323 AC: 683 AN: 2114

Alfa AF: 0.372 Hom.: 14556

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
PhyloP100		-0.36

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

Other links and lift over

dbSNP: rs17477949; hg19: chr11-12219203;