rs6809699

chr3-151338810-A-Cchr3-151338810-A-Gchr3-151338810-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0130

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]

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]

ACMG classification

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	UniProt
P2RY12	NM_022788.5	c.36T>G	p.Gly12=	synonymous_variant	3/3	ENST00000302632.4
MED12L	NM_001393769.1	c.2251-11249A>C		intron_variant		ENST00000687756.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133847 AN: 151958 Hom.: 59200 Cov.: 31

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

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.: 61 AF XY: 0.845 AC XY: 613838 AN XY: 726732

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.: 31 AF XY: 0.882 AC XY: 65583 AN XY: 74340

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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

Other links and lift over

dbSNP: rs6809699; hg19: chr3-151056598; COSMIC: COSV56380442; COSMIC: COSV56380442;