dbSNP rs758037994: MID2:c.1074-4delT (chrX-107915993-CT-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_012216.4(MID2):c.1074-4delT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00239 in 1,199,732 control chromosomes in the GnomAD database, including 4 homozygotes. There are 921 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., 60 hem., cov: 23)

Exomes 𝑓: 0.0024 ( 3 hom. 861 hem. )

Consequence

MID2
NM_012216.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.64

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant X-107915993-CT-C is Benign according to our data. Variant chrX-107915993-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 445463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 60 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4 link	c.1074-4delT		splice_region_variant, intron_variant	Intron 5 of 9	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.1074-8delT		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_012216.4	ENSP00000262843.6		Q9UJV3-1

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

204

AN:

111777

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000753

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00224

AC:

380

AN:

169336

AF XY:

0.00198

show subpopulations

Gnomad AFR exome

AF:

0.000318

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.000571

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00571

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.00245

AC:

2663

AN:

1087904

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

861

AN XY:

355736

show subpopulations

African (AFR)

AF:

0.000272

AC:

AN:

25757

American (AMR)

AF:

0.00143

AC:

AN:

32960

Ashkenazi Jewish (ASJ)

AF:

0.000680

AC:

AN:

19109

East Asian (EAS)

AF:

0.0000336

AC:

AN:

29797

South Asian (SAS)

AF:

0.0000578

AC:

AN:

51912

European-Finnish (FIN)

AF:

0.00475

AC:

191

AN:

40178

Middle Eastern (MID)

AF:

0.000488

AC:

AN:

4097

European-Non Finnish (NFE)

AF:

0.00273

AC:

2289

AN:

838458

Other (OTH)

AF:

0.00241

AC:

110

AN:

45636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00182

AC:

204

AN:

111828

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

AN XY:

34046

show subpopulations

African (AFR)

AF:

0.000422

AC:

AN:

30832

American (AMR)

AF:

0.000849

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.000753

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3564

South Asian (SAS)

AF:

0.00

AC:

AN:

2684

European-Finnish (FIN)

AF:

0.00518

AC:

AN:

5990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00281

AC:

149

AN:

53090

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000400

AC:

AN:

2512

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 24, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs758037994

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