4-155214524-C-G

Position:

• chr4-155214524-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000910.4(NPY2R):​c.585C>G​(p.Ile195Met) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06147322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.585C>G	p.Ile195Met	missense_variant	2/2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.585C>G	p.Ile195Met	missense_variant	2/2		NP_001357109.1
NPY2R	NM_001375470.1	c.585C>G	p.Ile195Met	missense_variant	2/2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.585C>G	p.Ile195Met	missense_variant	2/2	1	NM_000910.4	ENSP00000332591.3
NPY2R	ENST00000506608.1	c.585C>G	p.Ile195Met	missense_variant	2/2	1		ENSP00000426366.1
MAP9-AS1	ENST00000630664.2	n.208+40240C>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.75
DANN	Benign	0.92
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.68	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.060
Sift	Benign	0.24	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.13	B;B
Vest4		0.21
MutPred		0.55		Gain of glycosylation at S190 (P = 0.0391);Gain of glycosylation at S190 (P = 0.0391);
MVP		0.50
MPC		0.41
ClinPred		0.23	T
GERP RS		-6.2
Varity_R		0.061
gMVP		0.51

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

Other links and lift over

dbSNP: rs1047214; hg19: chr4-156135676;