chr19-53259246-C-A

Variant names:

• chr19-53259246-C-A
• NM_173856.2:c.871C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173856.2(VN1R2):​c.871C>A​(p.His291Asn) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VN1R2 NM_173856.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

Genes affected

VN1R2 (HGNC:19872): (vomeronasal 1 receptor 2) Predicted to enable pheromone receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VN1R2	NM_173856.2	c.871C>A	p.His291Asn	missense_variant	Exon 1 of 1	ENST00000341702.3	NP_776255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VN1R2	ENST00000341702.3	c.871C>A	p.His291Asn	missense_variant	Exon 1 of 1	6	NM_173856.2	ENSP00000351244.2
VN1R2	ENST00000598458.1	n.37C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.871C>A (p.H291N) alteration is located in exon 1 (coding exon 1) of the VN1R2 gene. This alteration results from a C to A substitution at nucleotide position 871, causing the histidine (H) at amino acid position 291 to be replaced by an asparagine (N). 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	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0034	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.90		Loss of catalytic residue at K292 (P = 0.0972);
MVP		0.40
MPC		0.61
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.81
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-53762499;