X-18999137-G-A

Position:

• chrX-18999137-G-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The ENST00000379869.8(ADGRG2):​c.2473C>T​(p.Arg825Ter) variant causes a stop gained 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ADGRG2 ENST00000379869.8 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.37

Genes affected

ADGRG2 (HGNC:4516): (adhesion G protein-coupled receptor G2) This gene encodes a member of the G protein-coupled receptor family described as an epididymis-specific transmembrane protein. The encoded protein may be proteolytically processed as it contains a motif shown to be a protein scission motif in some members of this family (PMID: 11973329). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-18999137-G-A is Pathogenic according to our data. Variant chrX-18999137-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 691628.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG2	NM_001079858.3	c.2473C>T	p.Arg825Ter	stop_gained	26/29	ENST00000379869.8	NP_001073327.1
LOC101928415	XR_001755805.2	n.755+10796G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8	c.2473C>T	p.Arg825Ter	stop_gained	26/29	1	NM_001079858.3	ENSP00000369198	A1
	ENST00000662768.1	n.229+14484G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital bilateral aplasia of vas deferens from CFTR mutation Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Biology Pathology Center, Lille University Hospital

Sep 01, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.65	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.48	N
MutationTaster	Benign	1.0	A;A;A;A;A;A;A;A;A;A
Vest4		0.45
GERP RS		-0.0039

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: rs1016696059; hg19: chrX-19017255; COSMIC: COSV61340629;