chr19-10113943-C-T

Position:

• chr19-10113943-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002566.5(P2RY11):​c.330C>T​(p.Thr110Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,602,540 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (8 hom.)
• Consequence: P2RY11 NM_002566.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.50

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-10113943-C-T is Benign according to our data. Variant chr19-10113943-C-T is described in ClinVar as [Benign]. Clinvar id is 725779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.51 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5	c.330C>T	p.Thr110Thr	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2
PPAN-P2RY11	NM_001040664.3	c.1590C>T	p.Thr530Thr	synonymous_variant	13/13		NP_001035754.1
PPAN-P2RY11	NM_001198690.2	c.*89C>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.330C>T	p.Thr110Thr	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4
PPAN-P2RY11	ENST00000393796.4	c.1590C>T	p.Thr530Thr	synonymous_variant	13/13	1		ENSP00000377385.4
PPAN-P2RY11	ENST00000428358.5	c.*89C>T		3_prime_UTR_variant	13/13	2		ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 325 AN: 152220 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00162 AC: 390 AN: 240190 Hom.: 1 AF XY: 0.00166 AC XY: 217 AN XY: 130850

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.000910

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.000801 AC: 1162 AN: 1450202 Hom.: 8 Cov.: 35 AF XY: 0.000806 AC XY: 582 AN XY: 721952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.000382

Gnomad4 OTH exome AF: 0.000746

GnomAD4 genome AF: 0.00213 AC: 325 AN: 152338 Hom.: 2 Cov.: 33 AF XY: 0.00326 AC XY: 243 AN XY: 74486

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000767 Hom.: 1

Bravo AF: 0.000276

EpiCase AF: 0.000491

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.1
DANN	Benign	0.96

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: rs142196416; hg19: chr19-10224619;