Genetic Variant NPY2R:p.Ile195Ile (chr4-155214524-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000910.4(NPY2R):c.585C>T(p.Ile195Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,613,844 control chromosomes in the GnomAD database, including 264,995 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 34015 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230980 hom. )

Consequence

NPY2R
NM_000910.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-1.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY2R	NM_000910.4 link	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	ENST00000329476.4	NP_000901.1	P49146
NPY2R	NM_001370180.1 link	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2		NP_001357109.1
NPY2R	NM_001375470.1 link	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPY2R	ENST00000329476.4 link	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	1	NM_000910.4	ENSP00000332591.3	P49146
NPY2R	ENST00000506608.1 link	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	1		ENSP00000426366.1	P49146
MAP9-AS1	ENST00000630664.2 link	n.208+40240C>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98713

AN:

151988

Hom.:

33975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.881

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.606

GnomAD3 exomes

AF:

0.578

AC:

145348

AN:

251388

Hom.:

43814

AF XY:

0.573

AC XY:

77886

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.888

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.798

Gnomad SAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.557

AC:

813610

AN:

1461738

Hom.:

230980

Cov.:

AF XY:

0.556

AC XY:

404092

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.898

Gnomad4 AMR exome

AF:

0.470

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.560

Gnomad4 FIN exome

AF:

0.618

Gnomad4 NFE exome

AF:

0.539

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.650

AC:

98809

AN:

152106

Hom.:

34015

Cov.:

AF XY:

0.651

AC XY:

48379

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.881

Gnomad4 AMR

AF:

0.516

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.572

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.557

Hom.:

47107

Bravo

AF:

0.649

Asia WGS

AF:

0.720

AC:

2502

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.91

DANN

Benign

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over