Variant 13-21502943-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_152726.3(MICU2):c.916A>T(p.Lys306*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00437 in 1,610,568 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 18 hom. )

Consequence

MICU2
NM_152726.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 13-21502943-T-A is Benign according to our data. Variant chr13-21502943-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 782571.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICU2	NM_152726.3 link	c.916A>T	p.Lys306*	stop_gained	9/12	ENST00000382374.9	NP_689939.1	Q8IYU8A0A0S2Z6V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MICU2	ENST00000382374.9 link	c.916A>T	p.Lys306*	stop_gained	9/12	1	NM_152726.3	ENSP00000371811.4	Q8IYU8
MICU2	ENST00000460488.5 link	n.156A>T		non_coding_transcript_exon_variant	1/3	3
MICU2	ENST00000479790.2 link	n.131A>T		non_coding_transcript_exon_variant	1/3	2
MICU2	ENST00000480341.5 link	n.447A>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

535

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00301

AC:

749

AN:

248452

Hom.:

AF XY:

0.00312

AC XY:

418

AN XY:

134084

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.000476

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00446

AC:

6506

AN:

1458276

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

3154

AN XY:

725144

show subpopulations

Gnomad4 AFR exome

AF:

0.000902

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000600

Gnomad4 FIN exome

AF:

0.000754

Gnomad4 NFE exome

AF:

0.00534

Gnomad4 OTH exome

AF:

0.00506

GnomAD4 genome

AF:

0.00351

AC:

535

AN:

152292

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00399

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00524

AC:

ExAC

AF:

0.00320

AC:

388

Asia WGS

AF:

0.000578

AC:

AN:

3474

EpiCase

AF:

0.00469

EpiControl

AF:

0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

MICU2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 13, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

Vest4

0.28

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.65

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.65

Position offset: -17

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