7-159036876-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003382.5(VIPR2):c.624C>G(p.Phe208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: VIPR2 NM_003382.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.643

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=0.23209813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR2	NM_003382.5	c.624C>G	p.Phe208Leu	missense_variant	7/13	ENST00000262178.7
VIPR2	NM_001308259.1	c.576C>G	p.Phe192Leu	missense_variant	4/10
VIPR2	NM_001304522.2	c.384C>G	p.Phe128Leu	missense_variant	5/11
VIPR2	NR_130758.2	n.720C>G		non_coding_transcript_exon_variant	7/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR2	ENST00000262178.7	c.624C>G	p.Phe208Leu	missense_variant	7/13	1	NM_003382.5	P2
VIPR2	ENST00000402066.5	c.1047C>G	p.Phe349Leu	missense_variant	7/13	5		A2
VIPR2	ENST00000377633.7	c.576C>G	p.Phe192Leu	missense_variant	4/10	2

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

Feb 22, 2023

The c.624C>G (p.F208L) alteration is located in exon 7 (coding exon 7) of the VIPR2 gene. This alteration results from a C to G substitution at nucleotide position 624, causing the phenylalanine (F) at amino acid position 208 to be replaced by a leucine (L). 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	0.46
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.33	T;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.084
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.42
MutPred		0.64		Loss of methylation at K203 (P = 0.1016);.;.;
MVP		0.061
MPC		0.23
ClinPred		0.44	T
GERP RS		-0.26
Varity_R		0.15
gMVP		0.13

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: chr7-158829567;