rs766333657

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022788.5(P2RY12):​c.805G>T​(p.Asp269Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D269N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

P2RY12
NM_022788.5 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.906
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
P2RY12NM_022788.5 linkc.805G>T p.Asp269Tyr missense_variant Exon 3 of 3 ENST00000302632.4 NP_073625.1 Q9H244A8K7T1
MED12LNM_001393769.1 linkc.2251-12018C>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
P2RY12ENST00000302632.4 linkc.805G>T p.Asp269Tyr missense_variant Exon 3 of 3 1 NM_022788.5 ENSP00000307259.4 Q9H244
MED12LENST00000687756.1 linkc.2251-12018C>A intron_variant Intron 16 of 44 NM_001393769.1 ENSP00000508695.1 A0A8I5KX78

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461798
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.57
D
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.24
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.94
P
Vest4
0.41
MutPred
0.75
Loss of solvent accessibility (P = 0.2517);
MVP
0.65
MPC
0.88
ClinPred
0.99
D
GERP RS
2.7
Varity_R
0.32
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-151055829; API