rs758037994

Variant names:

• chrX-107915993-CT-C
• rs758037994
• NM_012216.4:c.1074-4delT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000262843.11(MID2):​c.1074-8delT 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 ENST00000262843.11 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.64
• 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 -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 Benign/Likely_benign. ClinVar VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262843.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	NM_012216.4	MANE Select	c.1074-4delT		splice_region intron	N/A	NP_036348.2
	MID2	NM_001382751.1		c.1014-4delT		splice_region intron	N/A	NP_001369680.1
	MID2	NM_052817.3		c.1074-4delT		splice_region intron	N/A	NP_438112.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	ENST00000262843.11	TSL:1 MANE Select	c.1074-8delT		splice_region intron	N/A	ENSP00000262843.6
	MID2	ENST00000443968.2	TSL:1	c.1074-8delT		splice_region intron	N/A	ENSP00000413976.2
	ENSG00000236064	ENST00000430140.3	TSL:2	n.522+17036delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 204 AN: 111777 Hom.: 1 Cov.: 23

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

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.: 3 Cov.: 28 AF XY: 0.00242 AC XY: 861 AN XY: 355736

African (AFR) AF: 0.000272 AC: 7 AN: 25757

American (AMR) AF: 0.00143 AC: 47 AN: 32960

Ashkenazi Jewish (ASJ) AF: 0.000680 AC: 13 AN: 19109

East Asian (EAS) AF: 0.0000336 AC: 1 AN: 29797

South Asian (SAS) AF: 0.0000578 AC: 3 AN: 51912

European-Finnish (FIN) AF: 0.00475 AC: 191 AN: 40178

Middle Eastern (MID) AF: 0.000488 AC: 2 AN: 4097

European-Non Finnish (NFE) AF: 0.00273 AC: 2289 AN: 838458

Other (OTH) AF: 0.00241 AC: 110 AN: 45636

GnomAD4 genome AF: 0.00182 AC: 204 AN: 111828 Hom.: 1 Cov.: 23 AF XY: 0.00176 AC XY: 60 AN XY: 34046

African (AFR) AF: 0.000422 AC: 13 AN: 30832

American (AMR) AF: 0.000849 AC: 9 AN: 10601

Ashkenazi Jewish (ASJ) AF: 0.000753 AC: 2 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2684

European-Finnish (FIN) AF: 0.00518 AC: 31 AN: 5990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00281 AC: 149 AN: 53090

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.00262 Hom.: 24

Bravo AF: 0.00153

Asia WGS AF: 0.000400 AC: 1 AN: 2512

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs758037994; hg19: chrX-107159223;