dbSNP rs587777605: MID2:p.Arg347Gln (chrX-107905593-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP5BS2

The NM_012216.4(MID2):c.1040G>A(p.Arg347Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,088,323 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 10 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.68

Publications

5 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:

ENSG00000236064 (HGNC:):

ENSG00000236064 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP5

Variant X-107905593-G-A is Pathogenic according to our data. Variant chrX-107905593-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 143857.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 10 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4 link	c.1040G>A	p.Arg347Gln	missense_variant	Exon 5 of 10	ENST00000262843.11	NP_036348.2	Q9UJV3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11 link	c.1040G>A	p.Arg347Gln	missense_variant	Exon 5 of 10	1	NM_012216.4	ENSP00000262843.6		Q9UJV3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

175099

AF XY:

0.0000332

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1088323

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

354551

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26059

American (AMR)

AF:

0.00

AC:

AN:

34058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19026

East Asian (EAS)

AF:

0.00

AC:

AN:

29987

South Asian (SAS)

AF:

0.000292

AC:

AN:

51296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40347

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4100

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837756

Other (OTH)

AF:

0.00

AC:

AN:

45694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 101

Pathogenic:1

Jan 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Pathogenic

0.55

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

7.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.10

T;T

Sift4G

Benign

0.27

T;T

Polyphen

1.0

D;P

Vest4

0.26

MutPred

0.57

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.72

MPC

0.97

ClinPred

0.53

GERP RS

5.5

Varity_R

0.32

gMVP

0.60

Mutation Taster

=24/76

disease causing (ClinVar)

(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

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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