rs778859599

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_012216.4(MID2):c.491G>A(p.Arg164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,209,093 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 19 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, X-linked 101
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MID2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.320652).

BS2

High Hemizygotes in GnomAdExome4 at 19 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4 link	c.491G>A	p.Arg164His	missense_variant	Exon 2 of 10	ENST00000262843.11	NP_036348.2	Q9UJV3-1
MID2	NM_001382751.1 link	c.431G>A	p.Arg144His	missense_variant	Exon 2 of 10		NP_001369680.1
MID2	NM_052817.3 link	c.491G>A	p.Arg164His	missense_variant	Exon 2 of 10		NP_438112.2	Q9UJV3-2
MID2	NM_001382752.1 link	c.431G>A	p.Arg144His	missense_variant	Exon 2 of 10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MID2	ENST00000262843.11 link	c.491G>A	p.Arg164His	missense_variant	Exon 2 of 10	1	NM_012216.4	ENSP00000262843.6	Q9UJV3-1
MID2	ENST00000443968.2 link	c.491G>A	p.Arg164His	missense_variant	Exon 2 of 10	1		ENSP00000413976.2	Q9UJV3-2
MID2	ENST00000451923.1 link	c.431G>A	p.Arg144His	missense_variant	Exon 2 of 2	3		ENSP00000410730.1	A6PVI4

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111275

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000493

AC:

AN:

182515

AF XY:

0.0000596

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1097818

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363188

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19364

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.000351

AC:

AN:

54089

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40499

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000285

AC:

AN:

841865

Other (OTH)

AF:

0.0000434

AC:

AN:

46082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111275

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33467

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30566

American (AMR)

AF:

0.00

AC:

AN:

10552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3524

South Asian (SAS)

AF:

0.00

AC:

AN:

2564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

52991

Other (OTH)

AF:

0.00

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 101

Uncertain:1

Mar 05, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

0.41

MutationAssessor

Benign

1.9

.;L;L

PhyloP100

2.3

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.056

T;D;D

Polyphen

0.99, 0.98

.;D;D

Vest4

0.15, 0.34

MVP

0.83

MPC

1.5

ClinPred

0.22

GERP RS

5.9

Varity_R

0.51

gMVP

0.67

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over