4-155214054-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000910.4(NPY2R):c.115G>C(p.Glu39Gln) variant causes a missense change. 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: 32)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12571186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY2R	NM_000910.4	c.115G>C	p.Glu39Gln	missense_variant	2/2	ENST00000329476.4
NPY2R	NM_001370180.1	c.115G>C	p.Glu39Gln	missense_variant	2/2
NPY2R	NM_001375470.1	c.115G>C	p.Glu39Gln	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY2R	ENST00000329476.4	c.115G>C	p.Glu39Gln	missense_variant	2/2	1	NM_000910.4	P1
NPY2R	ENST00000506608.1	c.115G>C	p.Glu39Gln	missense_variant	2/2	1		P1
MAP9-AS1	ENST00000630664.2	n.208+39770G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Mar 23, 2022

The c.115G>C (p.E39Q) alteration is located in exon 2 (coding exon 1) of the NPY2R gene. This alteration results from a G to C substitution at nucleotide position 115, causing the glutamic acid (E) at amino acid position 39 to be replaced by a glutamine (Q). 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	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	16
Dann	Benign	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.045
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.044
Sift	Benign	0.26	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.17	B;B
Vest4		0.11
MutPred		0.25		Loss of glycosylation at P38 (P = 0.0264);Loss of glycosylation at P38 (P = 0.0264);
MVP		0.39
MPC		0.30
ClinPred		0.33	T
GERP RS		3.6
Varity_R		0.14
gMVP		0.41

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: chr4-156135206;