chr7-159035953-C-T

Position:

chr7-159035953-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003382.5(VIPR2):c.808G>A(p.Gly270Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000013 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VIPR2
NM_003382.5 missense, splice_region

Scores

Splicing: ADA: 0.7537

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

VIPR2 (HGNC:12695): (vasoactive intestinal peptide receptor 2) This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. [provided by RefSeq, Aug 2011]

VIPR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VIPR2	NM_003382.5 linkuse as main transcript	c.808G>A	p.Gly270Ser	missense_variant, splice_region_variant	8/13	ENST00000262178.7	NP_003373.2
VIPR2	NM_001308259.1 linkuse as main transcript	c.760G>A	p.Gly254Ser	missense_variant, splice_region_variant	5/10		NP_001295188.1
VIPR2	NM_001304522.2 linkuse as main transcript	c.568G>A	p.Gly190Ser	missense_variant, splice_region_variant	6/11		NP_001291451.1
VIPR2	NR_130758.2 linkuse as main transcript	n.904G>A		splice_region_variant, non_coding_transcript_exon_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPR2	ENST00000262178.7 linkuse as main transcript	c.808G>A	p.Gly270Ser	missense_variant, splice_region_variant	8/13	1	NM_003382.5	ENSP00000262178	P2	P41587-1
VIPR2	ENST00000402066.5 linkuse as main transcript	c.1231G>A	p.Gly411Ser	missense_variant, splice_region_variant	8/13	5		ENSP00000384497	A2
VIPR2	ENST00000377633.7 linkuse as main transcript	c.760G>A	p.Gly254Ser	missense_variant, splice_region_variant	5/10	2		ENSP00000366860		P41587-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250040

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461286

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 06, 2021

The c.808G>A (p.G270S) alteration is located in exon 8 (coding exon 8) of the VIPR2 gene. This alteration results from a G to A substitution at nucleotide position 808, causing the glycine (G) at amino acid position 270 to be replaced by a serine (S). 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

0.30

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;T;D

Sift4G

Uncertain

0.035

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.71

MutPred

0.74

Gain of glycosylation at G270 (P = 0.0137);.;.;

MVP

0.72

MPC

0.66

ClinPred

0.99

GERP RS

4.5

Varity_R

0.74

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.75

dbscSNV1_RF

Benign

0.56

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