19-10113961-C-T

Variant names:

• chr19-10113961-C-T
• rs79800334
• NM_002566.5:c.348C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 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.348C>T	p.Ser116Ser	synonymous	Exon 2 of 2	NP_002557.2
	PPAN-P2RY11	NM_001040664.3		c.1608C>T	p.Ser536Ser	synonymous	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8
	PPAN-P2RY11	NM_001198690.2		c.*107C>T		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.348C>T	p.Ser116Ser	synonymous	Exon 2 of 2	ENSP00000323872.4	Q96G91
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1608C>T	p.Ser536Ser	synonymous	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.*107C>T		3_prime_UTR	Exon 13 of 13	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

GnomAD2 exomes AF: 0.00826 AC: 1982 AN: 239960 AF XY: 0.0101

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 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

African (AFR) AF: 0.000269 AC: 9 AN: 33470

American (AMR) AF: 0.000604 AC: 27 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0309 AC: 1225 AN: 39690

South Asian (SAS) AF: 0.0455 AC: 3921 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41460

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.000145 AC: 161 AN: 1111830

Other (OTH) AF: 0.00720 AC: 434 AN: 60312

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

African (AFR) AF: 0.000361 AC: 15 AN: 41558

American (AMR) AF: 0.00274 AC: 42 AN: 15310

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

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5180

South Asian (SAS) AF: 0.0519 AC: 251 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68028

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

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

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
BayesDel_noAF	Benign	-0.33
CADD	Benign	6.8
DANN	Benign	0.95
PhyloP100		1.0
Mutation Taster		=93/7	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: rs79800334; hg19: chr19-10224637;