chr19-10113871-C-T

Variant names:

• chr19-10113871-C-T
• rs145464312
• NM_002566.5:c.258C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002566.5(P2RY11):​c.258C>T​(p.Ala86Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000851 in 1,610,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: P2RY11 NM_002566.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.95
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-10113871-C-T is Benign according to our data. Variant chr19-10113871-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 749577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.95 with no splicing effect.

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.258C>T	p.Ala86Ala	synonymous	Exon 2 of 2	NP_002557.2
	PPAN-P2RY11	NM_001040664.3		c.1518C>T	p.Ala506Ala	synonymous	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8
	PPAN-P2RY11	NM_001198690.2		c.*17C>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.258C>T	p.Ala86Ala	synonymous	Exon 2 of 2	ENSP00000323872.4	Q96G91
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1518C>T	p.Ala506Ala	synonymous	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.*17C>T		3_prime_UTR	Exon 13 of 13	ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152180 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000127 AC: 31 AN: 244664 AF XY: 0.000151

Gnomad AFR exome AF: 0.00163

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000555 AC: 81 AN: 1458464 Hom.: 0 Cov.: 36 AF XY: 0.0000413 AC XY: 30 AN XY: 725564

African (AFR) AF: 0.000867 AC: 29 AN: 33460

American (AMR) AF: 0.000112 AC: 5 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111266

Other (OTH) AF: 0.0000829 AC: 5 AN: 60316

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152298 Hom.: 0 Cov.: 34 AF XY: 0.000376 AC XY: 28 AN XY: 74466

African (AFR) AF: 0.00127 AC: 53 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000850 Hom.: 0

Bravo AF: 0.000404

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.077
DANN	Benign	0.94
PhyloP100		-3.9

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: rs145464312; hg19: chr19-10224547;