7-159030707-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

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]

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=0.18588781).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR2	ENST00000262178.7	c.1226C>T	p.Ser409Phe	missense_variant	13/13	1	NM_003382.5	P2
VIPR2	ENST00000402066.5	c.1649C>T	p.Ser550Phe	missense_variant	13/13	5		A2
VIPR2	ENST00000377633.7	c.1178C>T	p.Ser393Phe	missense_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1438632 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713610

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.: 33

Bravo AF: 0.00000378

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

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	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;.;T
Eigen	Benign	0.053
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.65	T
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	D
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

Other links and lift over

dbSNP: rs1853497399; hg19: chr7-158823398;