chr19-10114109-A-G

Variant names:

• chr19-10114109-A-G
• rs112371201
• NM_002566.5:c.496A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_002566.5(P2RY11):​c.496A>G​(p.Ser166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,600,876 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (5 hom.)
• Consequence: P2RY11 NM_002566.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.82
• Publications: 0 publications found

Genes affected

P2RY11 (HGNC:8540): (purinergic receptor P2Y11) 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 coupled to the stimulation of the phosphoinositide and adenylyl cyclase pathways and behaves as a selective purinoceptor. Naturally occuring read-through transcripts, resulting from intergenic splicing between this gene and an immediately upstream gene (PPAN, encoding peter pan homolog), have been found. The PPAN-P2RY11 read-through mRNA is ubiquitously expressed and encodes a fusion protein that shares identity with each individual gene product. [provided by RefSeq, Jul 2008]

PPAN-P2RY11 (HGNC:33526): (PPAN-P2RY11 readthrough) This locus represents naturally occurring read-through transcription between the adjacent PPAN and P2RY11 genes. Alternative splicing results in two transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This transcript is found to be ubiquitously expressed and is up-regulated by agents inducing granulocytic differentiation. However, its functional significance in vivo remains unclear. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009763926).
• BP6: Variant 19-10114109-A-G is Benign according to our data. Variant chr19-10114109-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3044892.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002566.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY11	NM_002566.5	MANE Select	c.496A>G	p.Ser166Gly	missense	Exon 2 of 2	NP_002557.2
	PPAN-P2RY11	NM_001040664.3		c.1756A>G	p.Ser586Gly	missense	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8
	PPAN-P2RY11	NM_001198690.2		c.*255A>G		3_prime_UTR	Exon 13 of 13	NP_001185619.1	A0A0A6YYI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY11	ENST00000321826.5	TSL:1 MANE Select	c.496A>G	p.Ser166Gly	missense	Exon 2 of 2	ENSP00000323872.4	Q96G91
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1756A>G	p.Ser586Gly	missense	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.*255A>G		3_prime_UTR	Exon 13 of 13	ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152154 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000573 AC: 134 AN: 233966 AF XY: 0.000476

Gnomad AFR exome AF: 0.00799

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000374

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000275 AC: 399 AN: 1448604 Hom.: 5 Cov.: 35 AF XY: 0.000251 AC XY: 181 AN XY: 721282

African (AFR) AF: 0.00926 AC: 310 AN: 33462

American (AMR) AF: 0.000157 AC: 7 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40790

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111628

Other (OTH) AF: 0.000680 AC: 41 AN: 60278

GnomAD4 genome AF: 0.00225 AC: 342 AN: 152272 Hom.: 1 Cov.: 34 AF XY: 0.00218 AC XY: 162 AN XY: 74470

African (AFR) AF: 0.00794 AC: 330 AN: 41574

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67986

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000575 Hom.: 0

Bravo AF: 0.00241

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000671 AC: 81

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	P2RY11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.11
DANN	Benign	0.93
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.53	N
PhyloP100		-1.8
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.071
Sift	Benign	0.24	T
Sift4G	Uncertain	0.033	D
Polyphen		0.0020	B
Vest4		0.074
MVP		0.19
MPC		0.050
ClinPred		0.0067	T
GERP RS		0.34
Varity_R		0.099
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs112371201; hg19: chr19-10224785;