rs150716868

Variant names:

• chrX-107926152-T-C
• rs150716868
• NM_012216.4:c.1656T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.919
• Publications: 0 publications found

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)

ENSG00000236064 (HGNC:):

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	NM_012216.4	MANE Select	c.1656T>C	p.Asp552Asp	synonymous	Exon 9 of 10	NP_036348.2	Q9UJV3-1
	MID2	NM_001382751.1		c.1596T>C	p.Asp532Asp	synonymous	Exon 9 of 10	NP_001369680.1
	MID2	NM_052817.3		c.1566T>C	p.Asp522Asp	synonymous	Exon 9 of 10	NP_438112.2	Q9UJV3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	ENST00000262843.11	TSL:1 MANE Select	c.1656T>C	p.Asp552Asp	synonymous	Exon 9 of 10	ENSP00000262843.6	Q9UJV3-1
	MID2	ENST00000443968.2	TSL:1	c.1566T>C	p.Asp522Asp	synonymous	Exon 9 of 10	ENSP00000413976.2	Q9UJV3-2
	MID2	ENST00000921443.1		c.1560T>C	p.Asp520Asp	synonymous	Exon 8 of 9	ENSP00000591502.1

Frequencies

GnomAD3 genomes AF: 0.000646 AC: 71 AN: 109972 Hom.: 0 Cov.: 22

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: 26 AN: 182856 AF XY: 0.0000742

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: 81 AN: 1094977 Hom.: 0 Cov.: 30 AF XY: 0.0000555 AC XY: 20 AN XY: 360577

African (AFR) AF: 0.00201 AC: 53 AN: 26320

American (AMR) AF: 0.000227 AC: 8 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30184

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40529

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839301

Other (OTH) AF: 0.000370 AC: 17 AN: 45974

GnomAD4 genome AF: 0.000654 AC: 72 AN: 110021 Hom.: 0 Cov.: 22 AF XY: 0.000525 AC XY: 17 AN XY: 32361

African (AFR) AF: 0.00228 AC: 69 AN: 30225

American (AMR) AF: 0.000194 AC: 2 AN: 10286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3509

South Asian (SAS) AF: 0.00 AC: 0 AN: 2506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5787

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52687

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.000304 Hom.: 1

Bravo AF: 0.000657

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.86
PhyloP100		0.92
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs150716868; hg19: chrX-107169382;