chr19-10113847-C-T

Variant names:

• chr19-10113847-C-T
• rs139458920
• NM_002566.5:c.234C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001198690.2(PPAN-P2RY11):​c.1556C>T​(p.Ala519Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,612,872 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (26 hom.)
• Consequence: PPAN-P2RY11 NM_001198690.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.55
• Publications: 5 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002979964).
• BP6: Variant 19-10113847-C-T is Benign according to our data. Variant chr19-10113847-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 773603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198690.2. 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.234C>T	p.Cys78Cys	synonymous	Exon 2 of 2	NP_002557.2
	PPAN-P2RY11	NM_001198690.2		c.1556C>T	p.Ala519Val	missense	Exon 13 of 13	NP_001185619.1	A0A0A6YYI3
	PPAN-P2RY11	NM_001040664.3		c.1494C>T	p.Cys498Cys	synonymous	Exon 13 of 13	NP_001035754.1	A0A0B4J1V8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY11	ENST00000321826.5	TSL:1 MANE Select	c.234C>T	p.Cys78Cys	synonymous	Exon 2 of 2	ENSP00000323872.4	Q96G91
	PPAN-P2RY11	ENST00000393796.4	TSL:1	c.1494C>T	p.Cys498Cys	synonymous	Exon 13 of 13	ENSP00000377385.4	A0A0B4J1V8
	PPAN-P2RY11	ENST00000428358.5	TSL:2	c.1556C>T	p.Ala519Val	missense	Exon 13 of 13	ENSP00000411918.1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 465 AN: 152172 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00481

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00346 AC: 851 AN: 246188 AF XY: 0.00345

Gnomad AFR exome AF: 0.000250

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.00530

Gnomad OTH exome AF: 0.00480

GnomAD4 exome AF: 0.00264 AC: 3856 AN: 1460582 Hom.: 26 Cov.: 32 AF XY: 0.00271 AC XY: 1969 AN XY: 726574

African (AFR) AF: 0.000299 AC: 10 AN: 33464

American (AMR) AF: 0.000314 AC: 14 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86214

European-Finnish (FIN) AF: 0.0106 AC: 561 AN: 52812

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

European-Non Finnish (NFE) AF: 0.00277 AC: 3077 AN: 1111562

Other (OTH) AF: 0.00252 AC: 152 AN: 60348

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152290 Hom.: 3 Cov.: 33 AF XY: 0.00328 AC XY: 244 AN XY: 74450

African (AFR) AF: 0.000120 AC: 5 AN: 41572

American (AMR) AF: 0.000262 AC: 4 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0109 AC: 116 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00481 AC: 327 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00402 Hom.: 11

Bravo AF: 0.00196

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00388 AC: 471

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	0.081
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.024
DANN	Uncertain	0.98
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.6
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MVP		0.030
ClinPred		0.022	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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: rs139458920; hg19: chr19-10224523; COSMIC: COSV53456314; COSMIC: COSV53456314;