13-21494973-C-G

Variant names:

• chr13-21494973-C-G
• rs1199941
• NM_152726.3:c.1200+188G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152726.3(MICU2):​c.1200+188G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,276 control chromosomes in the GnomAD database, including 68,860 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 0.95 (68860 hom., cov: 32)
• Consequence: MICU2 NM_152726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 0 publications found

Genes affected

MICU2 (HGNC:31830): (mitochondrial calcium uptake 2) Enables protein heterodimerization activity. Involved in calcium import into the mitochondrion and negative regulation of mitochondrial calcium ion concentration. Located in mitochondrial inner membrane and mitochondrial intermembrane space. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

MICU2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000291046 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICU2	NM_152726.3	c.1200+188G>C		intron_variant	Intron 11 of 11	ENST00000382374.9	NP_689939.1
MICU2	XM_047430142.1	c.930+188G>C		intron_variant	Intron 12 of 12		XP_047286098.1
MICU2	XM_017020433.2	c.654+188G>C		intron_variant	Intron 10 of 10		XP_016875922.1
MICU2	XM_047430143.1	c.*325G>C		downstream_gene_variant			XP_047286099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICU2	ENST00000382374.9	c.1200+188G>C		intron_variant	Intron 11 of 11	1	NM_152726.3	ENSP00000371811.4

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144577 AN: 152158 Hom.: 68821 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.950 AC: 144673 AN: 152276 Hom.: 68860 Cov.: 32 AF XY: 0.951 AC XY: 70842 AN XY: 74460

African (AFR) AF: 0.884 AC: 36735 AN: 41542

American (AMR) AF: 0.978 AC: 14950 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 3405 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.993 AC: 4795 AN: 4828

European-Finnish (FIN) AF: 0.953 AC: 10104 AN: 10598

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66289 AN: 68040

Other (OTH) AF: 0.957 AC: 2024 AN: 2114

Alfa AF: 0.958 Hom.: 3262

Bravo AF: 0.949

Asia WGS AF: 0.990 AC: 3438 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs1199941; hg19: chr13-22069112;