Variant chr13-21510028-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152726.3(MICU2):c.737A>G(p.Lys246Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,391,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MICU2
NM_152726.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4090515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU2	NM_152726.3 link	c.737A>G	p.Lys246Arg	missense_variant	8/12	ENST00000382374.9	NP_689939.1	Q8IYU8A0A0S2Z6V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MICU2	ENST00000382374.9 link	c.737A>G	p.Lys246Arg	missense_variant	8/12	1	NM_152726.3	ENSP00000371811.4	Q8IYU8
MICU2	ENST00000469058.1 link	n.829A>G		splice_region_variant, non_coding_transcript_exon_variant	9/9	5
MICU2	ENST00000476895.5 link	n.715A>G		splice_region_variant, non_coding_transcript_exon_variant	9/9	5
MICU2	ENST00000480341.5 link	n.268A>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1391596

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 09, 2024

The c.737A>G (p.K246R) alteration is located in exon 8 (coding exon 8) of the MICU2 gene. This alteration results from a A to G substitution at nucleotide position 737, causing the lysine (K) at amino acid position 246 to be replaced by an arginine (R). 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

Benign

0.10

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.017

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.7

REVEL

Benign

0.19

Sift

Uncertain

0.024

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.18

MutPred

0.34

Loss of methylation at K246 (P = 0.0281);

MVP

0.49

MPC

0.16

ClinPred

0.94

GERP RS

5.3

Varity_R

0.40

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over