Variant 4-155214810-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000910.4(NPY2R):c.871G>A(p.Val291Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,612,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

NPY2R
NM_000910.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

NPY2R (HGNC:7957): (neuropeptide Y receptor Y2) Predicted to enable calcium channel regulator activity and neuropeptide Y receptor activity. Involved in cardiac left ventricle morphogenesis and outflow tract morphogenesis. Located in cilium. Implicated in Huntington's disease; morbid obesity; and obesity. Biomarker of peripheral artery disease and temporal lobe epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPY2R links:

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

MAP9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0586586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4 link	c.871G>A	p.Val291Ile	missense_variant	2/2	ENST00000329476.4	NP_000901.1	P49146
NPY2R	NM_001370180.1 link	c.871G>A	p.Val291Ile	missense_variant	2/2		NP_001357109.1
NPY2R	NM_001375470.1 link	c.871G>A	p.Val291Ile	missense_variant	2/2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NPY2R	ENST00000329476.4 link	c.871G>A	p.Val291Ile	missense_variant	2/2	1	NM_000910.4	ENSP00000332591.3	P49146
NPY2R	ENST00000506608.1 link	c.871G>A	p.Val291Ile	missense_variant	2/2	1		ENSP00000426366.1	P49146
MAP9-AS1	ENST00000630664.2 link	n.208+40526G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250486

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1459912

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726010

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.871G>A (p.V291I) alteration is located in exon 2 (coding exon 1) of the NPY2R gene. This alteration results from a G to A substitution at nucleotide position 871, causing the valine (V) at amino acid position 291 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.090

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.090

Sift

Benign

0.25

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0040

B;B

Vest4

0.056

MVP

0.31

MPC

0.25

ClinPred

0.022

GERP RS

4.7

Varity_R

0.043

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over