dbSNP rs141574483: MID2:c.720+17G>A (chrX-107841402-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012216.4(MID2):c.720+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,107,863 control chromosomes in the GnomAD database, including 2 homozygotes. There are 259 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., 114 hem., cov: 23)

Exomes 𝑓: 0.00054 ( 0 hom. 145 hem. )

Consequence

MID2
NM_012216.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.460

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:

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=-0.95).

BP6

Variant X-107841402-G-A is Benign according to our data. Variant chrX-107841402-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 445781.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MID2	NM_012216.4	MANE Select	c.720+17G>A	intron	N/A	NP_036348.2	Q9UJV3-1
MID2	NM_001382751.1		c.660+17G>A	intron	N/A	NP_001369680.1
MID2	NM_052817.3		c.720+17G>A	intron	N/A	NP_438112.2	Q9UJV3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MID2	ENST00000262843.11	TSL:1 MANE Select	c.720+17G>A	intron	N/A	ENSP00000262843.6	Q9UJV3-1
MID2	ENST00000443968.2	TSL:1	c.720+17G>A	intron	N/A	ENSP00000413976.2	Q9UJV3-2
MID2	ENST00000921443.1		c.720+17G>A	intron	N/A	ENSP00000591502.1

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

389

AN:

111560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000854

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:

0.000132

Gnomad OTH

AF:

0.00601

GnomAD2 exomes

AF:

0.00136

AC:

201

AN:

147423

AF XY:

0.000880

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.000788

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000536

AC:

534

AN:

996248

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

145

AN XY:

287694

show subpopulations

African (AFR)

AF:

0.0104

AC:

249

AN:

23974

American (AMR)

AF:

0.000871

AC:

AN:

29842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16528

East Asian (EAS)

AF:

0.00

AC:

AN:

29586

South Asian (SAS)

AF:

0.0000434

AC:

AN:

46093

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38686

Middle Eastern (MID)

AF:

0.000793

AC:

AN:

3781

European-Non Finnish (NFE)

AF:

0.000242

AC:

185

AN:

765400

Other (OTH)

AF:

0.00163

AC:

AN:

42358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00357

AC:

399

AN:

111615

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

114

AN XY:

33851

show subpopulations

African (AFR)

AF:

0.0122

AC:

374

AN:

30700

American (AMR)

AF:

0.000853

AC:

AN:

10547

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

2605

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6073

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

53092

Other (OTH)

AF:

0.00593

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00258

Hom.:

Bravo

AF:

0.00435

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.12

(source)

DANN

Benign

0.73

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over