rs6809699

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022788.5(P2RY12):c.36T>G(p.Gly12=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-151338810-A-C is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY12	NM_022788.5 linkuse as main transcript	c.36T>G	p.Gly12=	synonymous_variant	3/3	ENST00000302632.4	NP_073625.1
MED12L	NM_001393769.1 linkuse as main transcript	c.2251-11249A>C		intron_variant		ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY12	ENST00000302632.4 linkuse as main transcript	c.36T>G	p.Gly12=	synonymous_variant	3/3	1	NM_022788.5	ENSP00000307259	P1
MED12L	ENST00000687756.1 linkuse as main transcript	c.2251-11249A>C		intron_variant			NM_001393769.1	ENSP00000508695	A2

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

GnomAD3 exomes

AF:

0.868

AC:

217850

AN:

250966

Hom.:

94810

AF XY:

0.867

AC XY:

117607

AN XY:

135636

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 SAS exome

AF:

0.901

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

Gnomad4 AFR exome

AF:

0.975

Gnomad4 AMR exome

AF:

0.893

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

0.879

Gnomad4 SAS exome

AF:

0.899

Gnomad4 FIN exome

AF:

0.840

Gnomad4 NFE exome

AF:

0.828

Gnomad4 OTH exome

AF:

0.861

GnomAD4 genome

AF:

0.881

AC:

133956

AN:

152076

Hom.:

59249

Cov.:

AF XY:

0.882

AC XY:

65583

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.881

Gnomad4 ASJ

AF:

0.879

Gnomad4 EAS

AF:

0.888

Gnomad4 SAS

AF:

0.901

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.833

Gnomad4 OTH

AF:

0.898

Alfa

AF:

0.857

Hom.:

27945

Bravo

AF:

0.888

Asia WGS

AF:

0.866

AC:

3013

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Platelet-type bleeding disorder 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.3

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over