Variant 4-155214986-T-G 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.1047T>G(p.Ile349Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

NPY2R
NM_000910.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.473

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=0.036458433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NPY2R	NM_000910.4 linkuse as main transcript	c.1047T>G	p.Ile349Met	missense_variant	2/2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1 linkuse as main transcript	c.1047T>G	p.Ile349Met	missense_variant	2/2		NP_001357109.1
NPY2R	NM_001375470.1 linkuse as main transcript	c.1047T>G	p.Ile349Met	missense_variant	2/2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NPY2R	ENST00000329476.4 linkuse as main transcript	c.1047T>G	p.Ile349Met	missense_variant	2/2	1	NM_000910.4	ENSP00000332591	P1
NPY2R	ENST00000506608.1 linkuse as main transcript	c.1047T>G	p.Ile349Met	missense_variant	2/2	1		ENSP00000426366	P1
MAP9-AS1	ENST00000630664.2 linkuse as main transcript	n.208+40702T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251340

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135838

show subpopulations

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:

0.000693

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000177

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000502

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

Jun 10, 2024

The c.1047T>G (p.I349M) alteration is located in exon 2 (coding exon 1) of the NPY2R gene. This alteration results from a T to G substitution at nucleotide position 1047, causing the isoleucine (I) at amino acid position 349 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.053

T;T

Polyphen

0.98

D;D

Vest4

0.14

MVP

0.52

MPC

0.32

ClinPred

0.094

GERP RS

-1.3

Varity_R

0.097

gMVP

0.49

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