4-155214578-C-A

Variant names:

• chr4-155214578-C-A
• rs1402216038
• NM_000910.4:c.639C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000910.4(NPY2R):​c.639C>A​(p.Ser213Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05346757).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000910.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	NM_000910.4	MANE Select	c.639C>A	p.Ser213Arg	missense	Exon 2 of 2	NP_000901.1	P49146
	NPY2R	NM_001370180.1		c.639C>A	p.Ser213Arg	missense	Exon 2 of 2	NP_001357109.1	P49146
	NPY2R	NM_001375470.1		c.639C>A	p.Ser213Arg	missense	Exon 2 of 2	NP_001362399.1	P49146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	ENST00000329476.4	TSL:1 MANE Select	c.639C>A	p.Ser213Arg	missense	Exon 2 of 2	ENSP00000332591.3	P49146
	NPY2R	ENST00000506608.1	TSL:1	c.639C>A	p.Ser213Arg	missense	Exon 2 of 2	ENSP00000426366.1	P49146
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+40294C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.97
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.81	N
REVEL	Benign	0.050
Sift	Benign	0.57	T
Sift4G	Benign	0.60	T
Polyphen		0.070	B
Vest4		0.14
MutPred		0.47		Loss of glycosylation at S213 (P = 0.0447)
MVP		0.25
MPC		0.39
ClinPred		0.16	T
GERP RS		3.1
Varity_R		0.052
gMVP		0.65
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1402216038; hg19: chr4-156135730;