Variant chr7-159031940-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_003382.5(VIPR2):c.1099C>A(p.Gln367Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VIPR2
NM_003382.5 missense, splice_region

Scores

Splicing: ADA: 0.9170

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.30

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VIPR2	NM_003382.5 linkuse as main transcript	c.1099C>A	p.Gln367Lys	missense_variant, splice_region_variant	11/13	ENST00000262178.7	NP_003373.2
VIPR2	NM_001308259.1 linkuse as main transcript	c.1051C>A	p.Gln351Lys	missense_variant, splice_region_variant	8/10		NP_001295188.1
VIPR2	NM_001304522.2 linkuse as main transcript	c.859C>A	p.Gln287Lys	missense_variant, splice_region_variant	9/11		NP_001291451.1
VIPR2	NR_130758.2 linkuse as main transcript	n.1195C>A		splice_region_variant, non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPR2	ENST00000262178.7 linkuse as main transcript	c.1099C>A	p.Gln367Lys	missense_variant, splice_region_variant	11/13	1	NM_003382.5	ENSP00000262178	P2	P41587-1
VIPR2	ENST00000402066.5 linkuse as main transcript	c.1522C>A	p.Gln508Lys	missense_variant, splice_region_variant	11/13	5		ENSP00000384497	A2
VIPR2	ENST00000377633.7 linkuse as main transcript	c.1051C>A	p.Gln351Lys	missense_variant, splice_region_variant	8/10	2		ENSP00000366860		P41587-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 11, 2022

The c.1099C>A (p.Q367K) alteration is located in exon 11 (coding exon 11) of the VIPR2 gene. This alteration results from a C to A substitution at nucleotide position 1099, causing the glutamine (Q) at amino acid position 367 to be replaced by a lysine (K). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;.;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.7

H;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.94

MutPred

0.85

Gain of methylation at Q367 (P = 0.0113);.;.;

MVP

0.45

MPC

0.84

ClinPred

1.0

GERP RS

5.1

Varity_R

0.84

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Pathogenic

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over