4-155214578-C-A

Position:

• chr4-155214578-C-A

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

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 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=0.05346757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.639C>A	p.Ser213Arg	missense_variant	2/2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.639C>A	p.Ser213Arg	missense_variant	2/2		NP_001357109.1
NPY2R	NM_001375470.1	c.639C>A	p.Ser213Arg	missense_variant	2/2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.639C>A	p.Ser213Arg	missense_variant	2/2	1	NM_000910.4	ENSP00000332591	P1
NPY2R	ENST00000506608.1	c.639C>A	p.Ser213Arg	missense_variant	2/2	1		ENSP00000426366	P1
MAP9-AS1	ENST00000630664.2	n.208+40294C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.639C>A (p.S213R) alteration is located in exon 2 (coding exon 1) of the NPY2R gene. This alteration results from a C to A substitution at nucleotide position 639, causing the serine (S) at amino acid position 213 to be replaced by an arginine (R). 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	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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.81	N;N
REVEL	Benign	0.050
Sift	Benign	0.57	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.070	B;B
Vest4		0.14
MutPred		0.47		Loss of glycosylation at S213 (P = 0.0447);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

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: chr4-156135730;