rs140237295

Variant names:

• chr19-10111734-G-A
• rs140237295
• NM_002566.5:c.13G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10111734-G-A
• chr19-10111734-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002566.5(P2RY11):​c.13G>A​(p.Val5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,652 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (107 hom.)
• Consequence: P2RY11 NM_002566.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01
• Publications: 1 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 (HGNC:9227): (peter pan homolog) The protein encoded by this gene is an evolutionarily conserved protein similar to yeast SSF1 as well as to the gene product of the Drosophila gene peter pan (ppan). SSF1 is known to be involved in the second step of mRNA splicing. Both SSF1 and ppan are essential for cell growth and proliferation. Exogenous expression of this gene was reported to reduce the anchorage-independent growth of some tumor cells. Read-through transcription of this gene with P2RY11/P2Y(11), an adjacent downstream gene that encodes an ATP receptor, has been found. These read-through transcripts are ubiquitously present and up-regulated during granulocyte differentiation. [provided by RefSeq, Nov 2010]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022428036).
• BP6: Variant 19-10111734-G-A is Benign according to our data. Variant chr19-10111734-G-A is described in ClinVar as Benign. ClinVar VariationId is 779371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

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.13G>A	p.Val5Ile	missense	Exon 1 of 2	NP_002557.2
	PPAN	NM_020230.7	MANE Select	c.*569G>A		3_prime_UTR	Exon 12 of 12	NP_064615.3
	PPAN	NM_001346139.1		c.*569G>A		3_prime_UTR	Exon 12 of 12	NP_001333068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY11	ENST00000321826.5	TSL:1 MANE Select	c.13G>A	p.Val5Ile	missense	Exon 1 of 2	ENSP00000323872.4	Q96G91
	PPAN	ENST00000253107.12	TSL:1 MANE Select	c.*569G>A		3_prime_UTR	Exon 12 of 12	ENSP00000253107.7	Q9NQ55-1
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1279+712G>A		intron	N/A	ENSP00000377385.4	A0A0B4J1V8

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 639 AN: 152112 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0110 AC: 2732 AN: 247408 AF XY: 0.00875

Gnomad AFR exome AF: 0.000743

Gnomad AMR exome AF: 0.0606

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0314

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000543

Gnomad OTH exome AF: 0.00608

GnomAD4 exome AF: 0.00238 AC: 3475 AN: 1461422 Hom.: 107 Cov.: 31 AF XY: 0.00205 AC XY: 1493 AN XY: 727004

African (AFR) AF: 0.000448 AC: 15 AN: 33472

American (AMR) AF: 0.0579 AC: 2588 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0150 AC: 597 AN: 39700

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111796

Other (OTH) AF: 0.00358 AC: 216 AN: 60368

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152230 Hom.: 12 Cov.: 32 AF XY: 0.00478 AC XY: 356 AN XY: 74444

African (AFR) AF: 0.000602 AC: 25 AN: 41524

American (AMR) AF: 0.0300 AC: 459 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5176

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.00141 Hom.: 7

Bravo AF: 0.00757

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00886 AC: 1075

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.052
DANN	Benign	0.64
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.0
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.014
Sift	Benign	0.61	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.042
MPC		0.027
ClinPred		0.000043	T
GERP RS		-1.5
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.021
gMVP		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs140237295; hg19: chr19-10222410; COSMIC: COSV108778803; COSMIC: COSV108778803;