Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022788.5(P2RY12):c.36T>G(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,612,836 control chromosomes in the GnomAD database, including 578,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59249 hom., cov: 31)

Exomes 𝑓: 0.84 ( 519592 hom. )

Consequence

P2RY12
NM_022788.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0130

Publications

66 publications found

Variant links:

Genes affected

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

P2RY12 links:

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L Gene-Disease associations (from GenCC):

Nizon-Isidor syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MED12L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 3-151338810-A-C is Benign according to our data. Variant chr3-151338810-A-C is described in ClinVar as Benign. ClinVar VariationId is 261633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022788.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P2RY12	NM_022788.5	MANE Select	c.36T>G	p.Gly12Gly	synonymous	Exon 3 of 3	NP_073625.1
MED12L	NM_001393769.1	MANE Select	c.2251-11249A>C		intron	N/A	NP_001380698.1
P2RY12	NM_176876.3		c.36T>G	p.Gly12Gly	synonymous	Exon 2 of 2	NP_795345.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.36T>G	p.Gly12Gly	synonymous	Exon 3 of 3	ENSP00000307259.4
P2RY12	ENST00000468596.1	TSL:1	n.308T>G		non_coding_transcript_exon	Exon 2 of 2
MED12L	ENST00000687756.1	MANE Select	c.2251-11249A>C		intron	N/A	ENSP00000508695.1

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

133847

AN:

151958

Hom.:

59200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.879

Gnomad EAS

AF:

0.888

Gnomad SAS

AF:

0.901

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.833

Gnomad OTH

AF:

0.901

GnomAD2 exomes

AF:

0.868

AC:

217850

AN:

250966

AF XY:

0.867

show subpopulations

Gnomad AFR exome

AF:

0.969

Gnomad AMR exome

AF:

0.894

Gnomad ASJ exome

AF:

0.884

Gnomad EAS exome

AF:

0.889

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.842

AC:

1230617

AN:

1460760

Hom.:

519592

Cov.:

AF XY:

0.845

AC XY:

613838

AN XY:

726732

show subpopulations

African (AFR)

AF:

0.975

AC:

32623

AN:

33468

American (AMR)

AF:

0.893

AC:

39909

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

23039

AN:

26130

East Asian (EAS)

AF:

0.879

AC:

34892

AN:

39696

South Asian (SAS)

AF:

0.899

AC:

77542

AN:

86234

European-Finnish (FIN)

AF:

0.840

AC:

44862

AN:

53396

Middle Eastern (MID)

AF:

0.956

AC:

5511

AN:

5766

European-Non Finnish (NFE)

AF:

0.828

AC:

920295

AN:

1111052

Other (OTH)

AF:

0.861

AC:

51944

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10007

20015

30022

40030

50037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21002

42004

63006

84008

105010

<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:

0.881

AC:

133956

AN:

152076

Hom.:

59249

Cov.:

AF XY:

0.882

AC XY:

65583

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.967

AC:

40121

AN:

41482

American (AMR)

AF:

0.881

AC:

13471

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.879

AC:

3050

AN:

3470

East Asian (EAS)

AF:

0.888

AC:

4584

AN:

5164

South Asian (SAS)

AF:

0.901

AC:

4321

AN:

4798

European-Finnish (FIN)

AF:

0.842

AC:

8910

AN:

10586

Middle Eastern (MID)

AF:

0.959

AC:

282

AN:

294

European-Non Finnish (NFE)

AF:

0.833

AC:

56634

AN:

67978

Other (OTH)

AF:

0.898

AC:

1894

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

800

1600

2401

3201

4001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.856

Hom.:

119341

Bravo

AF:

0.888

Asia WGS

AF:

0.866

AC:

3013

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Platelet-type bleeding disorder 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.3

(source)

DANN

Benign

0.62

PhyloP100

-0.013

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs6809699

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over