Genetic Variant NPY2R:p.Ile312Ile (chr4-155214875-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000910.4(NPY2R):c.936C>T(p.Ile312Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,610,122 control chromosomes in the GnomAD database, including 254,892 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 0.62 ( 29978 hom., cov: 33)

Exomes 𝑓: 0.55 ( 224914 hom. )

Consequence

NPY2R
NM_000910.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0910

Publications

24 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-0.091 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
NPY2R	NM_000910.4 link	c.936C>T	p.Ile312Ile	synonymous_variant	Exon 2 of 2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1 link	c.936C>T	p.Ile312Ile	synonymous_variant	Exon 2 of 2		NP_001357109.1
NPY2R	NM_001375470.1 link	c.936C>T	p.Ile312Ile	synonymous_variant	Exon 2 of 2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
NPY2R	ENST00000329476.4 link	c.936C>T	p.Ile312Ile	synonymous_variant	Exon 2 of 2	1	NM_000910.4	ENSP00000332591.3
NPY2R	ENST00000506608.1 link	c.936C>T	p.Ile312Ile	synonymous_variant	Exon 2 of 2	1		ENSP00000426366.1
MAP9-AS1	ENST00000630664.3 link	n.399+40591C>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93739

AN:

152042

Hom.:

29954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.576

GnomAD2 exomes

AF:

0.566

AC:

141447

AN:

249784

AF XY:

0.564

show subpopulations

Gnomad AFR exome

AF:

0.781

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.753

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.542

GnomAD4 exome

AF:

0.552

AC:

804191

AN:

1457962

Hom.:

224914

Cov.:

AF XY:

0.551

AC XY:

399314

AN XY:

724732

show subpopulations

African (AFR)

AF:

0.790

AC:

26303

AN:

33290

American (AMR)

AF:

0.463

AC:

20559

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

12625

AN:

25956

East Asian (EAS)

AF:

0.756

AC:

29975

AN:

39636

South Asian (SAS)

AF:

0.555

AC:

47724

AN:

85972

European-Finnish (FIN)

AF:

0.617

AC:

32913

AN:

53306

Middle Eastern (MID)

AF:

0.523

AC:

3003

AN:

5742

European-Non Finnish (NFE)

AF:

0.539

AC:

597614

AN:

1109414

Other (OTH)

AF:

0.556

AC:

33475

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

22258

44516

66775

89033

111291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17078

34156

51234

68312

85390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.617

AC:

93813

AN:

152160

Hom.:

29978

Cov.:

AF XY:

0.618

AC XY:

45967

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.774

AC:

32157

AN:

41520

American (AMR)

AF:

0.503

AC:

7683

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1692

AN:

3468

East Asian (EAS)

AF:

0.753

AC:

3891

AN:

5166

South Asian (SAS)

AF:

0.564

AC:

2717

AN:

4818

European-Finnish (FIN)

AF:

0.626

AC:

6641

AN:

10602

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.545

AC:

37027

AN:

67988

Other (OTH)

AF:

0.581

AC:

1223

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1777

3554

5332

7109

8886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.572

Hom.:

13445

Bravo

AF:

0.611

Asia WGS

AF:

0.697

AC:

2425

AN:

3478

EpiCase

AF:

0.527

EpiControl

AF:

0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.7

(source)

DANN

Benign

0.62

PhyloP100

-0.091

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over