rs6785930

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.18C>T(p.Asn6Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,610,536 control chromosomes in the GnomAD database, including 74,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5847 hom., cov: 31)

Exomes 𝑓: 0.31 ( 69141 hom. )

Consequence

P2RY12
NM_022788.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.08

Publications

68 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=-0.51).

BP6

Variant 3-151338828-G-A is Benign according to our data. Variant chr3-151338828-G-A is described in ClinVar as Benign. ClinVar VariationId is 261632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY12	NM_022788.5 link	c.18C>T	p.Asn6Asn	synonymous_variant	Exon 3 of 3	ENST00000302632.4	NP_073625.1	Q9H244A8K7T1
MED12L	NM_001393769.1 link	c.2251-11231G>A		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY12	ENST00000302632.4 link	c.18C>T	p.Asn6Asn	synonymous_variant	Exon 3 of 3	1	NM_022788.5	ENSP00000307259.4		Q9H244
MED12L	ENST00000687756.1 link	c.2251-11231G>A		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1		A0A8I5KX78

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41154

AN:

151804

Hom.:

5848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.295

AC:

73921

AN:

250832

AF XY:

0.296

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.305

AC:

445058

AN:

1458612

Hom.:

69141

Cov.:

AF XY:

0.306

AC XY:

221828

AN XY:

725744

show subpopulations

African (AFR)

AF:

0.175

AC:

5841

AN:

33432

American (AMR)

AF:

0.320

AC:

14267

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

5169

AN:

26122

East Asian (EAS)

AF:

0.240

AC:

9535

AN:

39680

South Asian (SAS)

AF:

0.296

AC:

25548

AN:

86188

European-Finnish (FIN)

AF:

0.368

AC:

19667

AN:

53380

Middle Eastern (MID)

AF:

0.271

AC:

1559

AN:

5762

European-Non Finnish (NFE)

AF:

0.312

AC:

345965

AN:

1109100

Other (OTH)

AF:

0.290

AC:

17507

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

16478

32956

49434

65912

82390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11250

22500

33750

45000

56250

<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:

0.271

AC:

41170

AN:

151924

Hom.:

5847

Cov.:

AF XY:

0.273

AC XY:

20291

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.184

AC:

7619

AN:

41432

American (AMR)

AF:

0.295

AC:

4500

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

676

AN:

3466

East Asian (EAS)

AF:

0.222

AC:

1143

AN:

5160

South Asian (SAS)

AF:

0.302

AC:

1448

AN:

4802

European-Finnish (FIN)

AF:

0.366

AC:

3859

AN:

10554

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21045

AN:

67948

Other (OTH)

AF:

0.274

AC:

577

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1490

2980

4471

5961

7451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.287

Hom.:

13478

Bravo

AF:

0.259

Asia WGS

AF:

0.245

AC:

852

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.9

(source)

DANN

Benign

0.69

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over