Variant 13-21493304-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152726.3(MICU2):c.1250A>C(p.Glu417Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MICU2
NM_152726.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU2	NM_152726.3 link	c.1250A>C	p.Glu417Ala	missense_variant	12/12	ENST00000382374.9	NP_689939.1	Q8IYU8A0A0S2Z6V5
MICU2	XM_047430142.1 link	c.980A>C	p.Glu327Ala	missense_variant	13/13		XP_047286098.1
MICU2	XM_017020433.2 link	c.704A>C	p.Glu235Ala	missense_variant	11/11		XP_016875922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MICU2	ENST00000382374.9 link	c.1250A>C	p.Glu417Ala	missense_variant	12/12	1	NM_152726.3	ENSP00000371811.4	Q8IYU8
MICU2	ENST00000460488.5 link	n.381A>C		non_coding_transcript_exon_variant	3/3	3
MICU2	ENST00000478700.1 link	n.809A>C		non_coding_transcript_exon_variant	3/3	2
MICU2	ENST00000479790.2 link	n.1198A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458960

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1250A>C (p.E417A) alteration is located in exon 12 (coding exon 12) of the MICU2 gene. This alteration results from a A to C substitution at nucleotide position 1250, causing the glutamic acid (E) at amino acid position 417 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.69

MutPred

0.46

Loss of loop (P = 0.0512);

MVP

0.65

MPC

0.50

ClinPred

0.99

GERP RS

5.9

Varity_R

0.68

gMVP

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over