MED25 p.Pro217Pro

Variant names:

• chr19-49829908-C-C
• ENST00000312865.10:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-49829909--
• chr19-49829911-G-T
• chr19-49829911-G-C
• chr19-49829911-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000312865.10(MED25):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED25 ENST00000312865.10 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

Genes affected

MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

MED25 Gene-Disease associations (from GenCC):

• congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 2B2

  Inheritance: AR Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000312865.10. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED25	ENST00000312865.10	TSL:1 MANE Select	c.		exon_region	Exon 6 of 18	ENSP00000326767.5	Q71SY5-1
	MED25	ENST00000595185.5	TSL:1	c.		exon_region	Exon 6 of 7	ENSP00000470027.1	M0QYR4
	MED25	ENST00000538643.5	TSL:1	c.		intron	N/A	ENSP00000437496.1	Q71SY5-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-50333165;