Variant 19-53258844-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173856.2(VN1R2):c.469G>T(p.Asp157Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

VN1R2
NM_173856.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.874

Variant links:

Genes affected

VN1R2 (HGNC:19872): (vomeronasal 1 receptor 2) Predicted to enable pheromone receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VN1R2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.020857751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VN1R2	NM_173856.2 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	1/1	ENST00000341702.3	NP_776255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VN1R2	ENST00000341702.3 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	1/1		NM_173856.2	ENSP00000351244	P1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000506

AC:

127

AN:

250930

Hom.:

AF XY:

0.000501

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000942

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000565

AC:

826

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

388

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000697

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000447

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000804

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000535

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.469G>T (p.D157Y) alteration is located in exon 1 (coding exon 1) of the VN1R2 gene. This alteration results from a G to T substitution at nucleotide position 469, causing the aspartic acid (D) at amino acid position 157 to be replaced by a tyrosine (Y). 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

0.072

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.032

DANN

Benign

0.34

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.34

M_CAP

Benign

0.0016

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

1.8

REVEL

Benign

0.13

Sift

Benign

0.57

Sift4G

Benign

0.83

Polyphen

0.65

Vest4

0.14

MVP

0.19

MPC

0.17

ClinPred

0.020

GERP RS

-5.9

Varity_R

0.029

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over