Genetic Variant MED15:p.Gln216_Gln218dup (chr22-20564628-C-CCAGCAGCAG) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_001003891.3(MED15):c.648_656dupGCAGCAGCA(p.Gln216_Gln218dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 150,978 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MED15
NM_001003891.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.48

Publications

6 publications found

Variant links:

Genes affected

MED15 (HGNC:14248): (mediator complex subunit 15) The protein encoded by this gene is a subunit of the multiprotein complexes PC2 and ARC/DRIP and may function as a transcriptional coactivator in RNA polymerase II transcription. This gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

MED15 links:

ENSG00000307622 (HGNC:):

ENSG00000307622 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001003891.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003891.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED15	NM_001003891.3	MANE Select	c.648_656dupGCAGCAGCA	p.Gln216_Gln218dup	disruptive_inframe_insertion	Exon 6 of 18	NP_001003891.1	Q96RN5-1
MED15	NM_015889.5		c.648_656dupGCAGCAGCA	p.Gln216_Gln218dup	disruptive_inframe_insertion	Exon 6 of 17	NP_056973.2
MED15	NM_001293234.2		c.648_656dupGCAGCAGCA	p.Gln216_Gln218dup	disruptive_inframe_insertion	Exon 6 of 17	NP_001280163.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED15	ENST00000263205.11	TSL:1 MANE Select	c.648_656dupGCAGCAGCA	p.Gln216_Gln218dup	disruptive_inframe_insertion	Exon 6 of 18	ENSP00000263205.7	Q96RN5-1
MED15	ENST00000292733.11	TSL:1	c.648_656dupGCAGCAGCA	p.Gln216_Gln218dup	disruptive_inframe_insertion	Exon 6 of 17	ENSP00000292733.7	Q96RN5-2
MED15	ENST00000406969.5	TSL:1	c.570_578dupGCAGCAGCA	p.Gln190_Gln192dup	disruptive_inframe_insertion	Exon 6 of 17	ENSP00000384344.1	G3V1P5

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

150978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000268

AC:

AN:

1455604

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33234

American (AMR)

AF:

0.00

AC:

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000758

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

85784

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

53048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000316

AC:

AN:

1107512

Other (OTH)

AF:

0.00

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00000662

AC:

AN:

150978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40994

American (AMR)

AF:

0.00

AC:

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67670

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=76/24

polymorphism

(source)

Splicing

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

Publications

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22-20564628-CCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over