dbSNP rs150716868: MID2:p.Asp552Asp (chrX-107926152-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_012216.4(MID2):c.1656T>C(p.Asp552Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,204,998 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., 17 hem., cov: 22)

Exomes 𝑓: 0.000074 ( 0 hom. 20 hem. )

Consequence

MID2
NM_012216.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.919

Publications

0 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-107926152-T-C is Benign according to our data. Variant chrX-107926152-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435869.

BP7

Synonymous conserved (PhyloP=0.919 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 17 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4 link	c.1656T>C	p.Asp552Asp	synonymous_variant	Exon 9 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.1656T>C	p.Asp552Asp	synonymous_variant	Exon 9 of 10	1	NM_012216.4	ENSP00000262843.6		Q9UJV3-1

Frequencies

GnomAD3 genomes

AF:

0.000646

AC:

AN:

109972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000195

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000142

AC:

AN:

182856

AF XY:

0.0000742

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.000110

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:

0.0000740

AC:

AN:

1094977

Hom.:

Cov.:

AF XY:

0.0000555

AC XY:

AN XY:

360577

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

26320

American (AMR)

AF:

0.000227

AC:

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19354

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40529

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

839301

Other (OTH)

AF:

0.000370

AC:

AN:

45974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000654

AC:

AN:

110021

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

32361

show subpopulations

African (AFR)

AF:

0.00228

AC:

AN:

30225

American (AMR)

AF:

0.000194

AC:

AN:

10286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2630

East Asian (EAS)

AF:

0.00

AC:

AN:

3509

South Asian (SAS)

AF:

0.00

AC:

AN:

2506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5787

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52687

Other (OTH)

AF:

0.00

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000657

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

(source)

DANN

Benign

0.86

PhyloP100

0.92

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over