Variant chr4-155214453-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000910.4(NPY2R):c.514G>A(p.Ala172Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000533 in 1,614,050 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 10 hom. )

Consequence

NPY2R
NM_000910.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.24

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:):

MAP9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009547472).

BP6

Variant 4-155214453-G-A is Benign according to our data. Variant chr4-155214453-G-A is described in ClinVar as [Benign]. Clinvar id is 778315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	2/2	ENST00000329476.4	NP_000901.1	P49146
NPY2R	NM_001370180.1 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	2/2		NP_001357109.1
NPY2R	NM_001375470.1 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	2/2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NPY2R	ENST00000329476.4 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	2/2	1	NM_000910.4	ENSP00000332591.3	P49146
NPY2R	ENST00000506608.1 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	2/2	1		ENSP00000426366.1	P49146
MAP9-AS1	ENST00000630664.2 linkuse as main transcript	n.208+40169G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00230

AC:

578

AN:

251038

Hom.:

AF XY:

0.00164

AC XY:

222

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000503

AC:

736

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

298

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152238

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.00149

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 01, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

.;D

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.84

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.11

Sift

Benign

0.69

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.010

B;B

Vest4

0.15

MVP

0.63

MPC

0.30

ClinPred

0.024

GERP RS

5.7

Varity_R

0.13

gMVP

0.48

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