Variant X-107841204-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_012216.4(MID2):c.539G>A(p.Arg180His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,098,190 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 8 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

MID2 (HGNC:7096): (midline 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]

MID2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.744

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID2	NM_012216.4 linkuse as main transcript	c.539G>A	p.Arg180His	missense_variant	2/10	ENST00000262843.11	NP_036348.2	Q9UJV3-1
MID2	NM_001382751.1 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.539G>A	p.Arg180His	missense_variant	2/10		NP_438112.2	Q9UJV3-2
MID2	NM_001382752.1 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	2/10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MID2	ENST00000262843.11 linkuse as main transcript	c.539G>A	p.Arg180His	missense_variant	2/10	1	NM_012216.4	ENSP00000262843.6	Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.539G>A	p.Arg180His	missense_variant	2/10	1		ENSP00000413976.2	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.479G>A	p.Arg160His	missense_variant	2/2	3		ENSP00000410730.1	A6PVI4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183160

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1098190

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363544

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:

0.0000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Dec 06, 2024

The c.539G>A (p.R180H) alteration is located in exon 2 (coding exon 2) of the MID2 gene. This alteration results from a G to A substitution at nucleotide position 539, causing the arginine (R) at amino acid position 180 to be replaced by a histidine (H). 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

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.057

T;T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.72

MetaRNN

Pathogenic

0.74

D;D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

3.0

.;M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Uncertain

0.64

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.036

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.60, 0.66

MutPred

0.39

.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);

MVP

0.97

MPC

1.5

ClinPred

0.92

GERP RS

5.9

Varity_R

0.54

gMVP

0.62

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