19-10113961-C-T

Position:

• chr19-10113961-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002566.5(P2RY11):​c.348C>T​(p.Ser116Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,601,950 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (13 hom., cov: 34)
  • Exomes 𝑓: 0.0040 (177 hom.)
• Consequence: P2RY11 NM_002566.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 19-10113961-C-T is Benign according to our data. Variant chr19-10113961-C-T is described in ClinVar as [Benign]. Clinvar id is 779032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00301 (459/152332) while in subpopulation SAS AF= 0.0519 (251/4832). AF 95% confidence interval is 0.0467. There are 13 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5	c.348C>T	p.Ser116Ser	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2
PPAN-P2RY11	NM_001040664.3	c.1608C>T	p.Ser536Ser	synonymous_variant	13/13		NP_001035754.1
PPAN-P2RY11	NM_001198690.2	c.*107C>T		3_prime_UTR_variant	13/13		NP_001185619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY11	ENST00000321826.5	c.348C>T	p.Ser116Ser	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4
PPAN-P2RY11	ENST00000393796.4	c.1608C>T	p.Ser536Ser	synonymous_variant	13/13	1		ENSP00000377385.4
PPAN-P2RY11	ENST00000428358.5	c.*107C>T		3_prime_UTR_variant	13/13	2		ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 461 AN: 152214 Hom.: 13 Cov.: 34

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00826 AC: 1982 AN: 239960 Hom.: 56 AF XY: 0.0101 AC XY: 1327 AN XY: 130746

Gnomad AFR exome AF: 0.000683

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0244

Gnomad SAS exome AF: 0.0468

Gnomad FIN exome AF: 0.0000750

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00545

GnomAD4 exome AF: 0.00399 AC: 5785 AN: 1449618 Hom.: 177 Cov.: 35 AF XY: 0.00518 AC XY: 3735 AN XY: 721674

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0309

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00720

GnomAD4 genome AF: 0.00301 AC: 459 AN: 152332 Hom.: 13 Cov.: 34 AF XY: 0.00375 AC XY: 279 AN XY: 74484

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000567 Hom.: 0

Bravo AF: 0.00167

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	6.8
DANN	Benign	0.95

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: rs79800334; hg19: chr19-10224637;