chr19-10114018-C-T

Position:

• chr19-10114018-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002566.5(P2RY11):​c.405C>T​(p.Phe135Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: P2RY11 NM_002566.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.609

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-10114018-C-T is Benign according to our data. Variant chr19-10114018-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 758149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.609 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY11	NM_002566.5	c.405C>T	p.Phe135Phe	synonymous_variant	2/2	ENST00000321826.5	NP_002557.2
PPAN-P2RY11	NM_001040664.3	c.1665C>T	p.Phe555Phe	synonymous_variant	13/13		NP_001035754.1
PPAN-P2RY11	NM_001198690.2	c.*164C>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.405C>T	p.Phe135Phe	synonymous_variant	2/2	1	NM_002566.5	ENSP00000323872.4
PPAN-P2RY11	ENST00000393796.4	c.1665C>T	p.Phe555Phe	synonymous_variant	13/13	1		ENSP00000377385.4
PPAN-P2RY11	ENST00000428358.5	c.*164C>T		3_prime_UTR_variant	13/13	2		ENSP00000411918.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.1
DANN	Benign	0.89

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: rs1599321205; hg19: chr19-10224694;