X-107841402-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 445781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID2	NM_012216.4	c.720+17G>A		intron_variant		ENST00000262843.11
MID2	NM_001382751.1	c.660+17G>A		intron_variant
MID2	NM_001382752.1	c.660+17G>A		intron_variant
MID2	NM_052817.3	c.720+17G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID2	ENST00000262843.11	c.720+17G>A		intron_variant		1	NM_012216.4
MID2	ENST00000443968.2	c.720+17G>A		intron_variant		1		P1
MID2	ENST00000451923.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00349 AC: 389 AN: 111560 Hom.: 2 Cov.: 23 AF XY: 0.00314 AC XY: 106 AN XY: 33786

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

GnomAD3 exomes AF: 0.00136 AC: 201 AN: 147423 Hom.: 0 AF XY: 0.000880 AC XY: 41 AN XY: 46597

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 SAS exome AF: 0.0000869

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.: 0 Cov.: 21 AF XY: 0.000504 AC XY: 145 AN XY: 287694

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.000871

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000434

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000242

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00357 AC: 399 AN: 111615 Hom.: 2 Cov.: 23 AF XY: 0.00337 AC XY: 114 AN XY: 33851

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.000853

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00593

Alfa AF: 0.00258 Hom.: 16

Bravo AF: 0.00435

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Jun 15, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.12
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs141574483; hg19: chrX-107084632;