7-159103785-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003382.5(VIPR2):c.329G>A(p.Gly110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VIPR2 NM_003382.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR2	NM_003382.5	c.329G>A	p.Gly110Asp	missense_variant	4/13	ENST00000262178.7
VIPR2	NM_001304522.2	c.329G>A	p.Gly110Asp	missense_variant	4/11
VIPR2	NR_130758.2	n.425G>A		non_coding_transcript_exon_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR2	ENST00000262178.7	c.329G>A	p.Gly110Asp	missense_variant	4/13	1	NM_003382.5	P2
VIPR2	ENST00000402066.5	c.752G>A	p.Gly251Asp	missense_variant	4/13	5		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Mar 21, 2023

The c.329G>A (p.G110D) alteration is located in exon 4 (coding exon 4) of the VIPR2 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the glycine (G) at amino acid position 110 to be replaced by an aspartic acid (D). 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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.065	T;T
Polyphen		0.92	P;.
Vest4		0.72
MutPred		0.44		Gain of disorder (P = 0.0898);.;
MVP		0.41
MPC		0.76
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.79
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-158896476;