Variant 7-159030707-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003382.5(VIPR2):c.1226C>T(p.Ser409Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000348 in 1,438,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

VIPR2
NM_003382.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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:

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ACMG classification

Classification made for transcript

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=0.18588781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPR2	NM_003382.5 link	c.1226C>T	p.Ser409Phe	missense_variant	13/13	ENST00000262178.7	NP_003373.2	P41587-1X5D7Q6
VIPR2	NM_001308259.1 link	c.1178C>T	p.Ser393Phe	missense_variant	10/10		NP_001295188.1	P41587-2
VIPR2	NM_001304522.2 link	c.986C>T	p.Ser329Phe	missense_variant	11/11		NP_001291451.1	P41587X5DP12
VIPR2	NR_130758.2 link	n.1656C>T		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VIPR2	ENST00000262178.7 link	c.1226C>T	p.Ser409Phe	missense_variant	13/13	1	NM_003382.5	ENSP00000262178.2	P41587-1
VIPR2	ENST00000402066.5 link	c.1649C>T	p.Ser550Phe	missense_variant	13/13	5		ENSP00000384497.1	C9JCP7
VIPR2	ENST00000377633.7 link	c.1178C>T	p.Ser393Phe	missense_variant	10/10	2		ENSP00000366860.3	P41587-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1438632

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713610

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:

0.00000363

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 08, 2022

The c.1226C>T (p.S409F) alteration is located in exon 13 (coding exon 13) of the VIPR2 gene. This alteration results from a C to T substitution at nucleotide position 1226, causing the serine (S) at amino acid position 409 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;.;T

Eigen

Benign

0.053

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.48

P;.;.

Vest4

0.13

MutPred

0.35

Loss of phosphorylation at S409 (P = 0.0242);.;.;

MVP

0.68

MPC

0.76

ClinPred

0.99

GERP RS

5.2

Varity_R

0.60

gMVP

0.49

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