4-155214400-A-G

Variant names:

• chr4-155214400-A-G
• NM_000910.4:c.461A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000910.4(NPY2R):​c.461A>G​(p.Tyr154Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.461A>G	p.Tyr154Cys	missense_variant	Exon 2 of 2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.461A>G	p.Tyr154Cys	missense_variant	Exon 2 of 2		NP_001357109.1
NPY2R	NM_001375470.1	c.461A>G	p.Tyr154Cys	missense_variant	Exon 2 of 2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.461A>G	p.Tyr154Cys	missense_variant	Exon 2 of 2	1	NM_000910.4	ENSP00000332591.3
NPY2R	ENST00000506608.1	c.461A>G	p.Tyr154Cys	missense_variant	Exon 2 of 2	1		ENSP00000426366.1
MAP9-AS1	ENST00000630664.2	n.208+40116A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461A>G (p.Y154C) alteration is located in exon 2 (coding exon 1) of the NPY2R gene. This alteration results from a A to G substitution at nucleotide position 461, causing the tyrosine (Y) at amino acid position 154 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.67		Loss of methylation at K159 (P = 0.0554);Loss of methylation at K159 (P = 0.0554);
MVP		0.69
MPC		1.1
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-156135552;