chrX-19003070-CACAG-TCT

Variant names:

• chrX-19003070-CACAG-TCT
• rs879255539
• NM_001079858.3:c.2002_2006delCTGTGinsAGA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001079858.3(ADGRG2):​c.2002_2006delCTGTGinsAGA​(p.Leu668ArgfsTer21) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ADGRG2 NM_001079858.3 frameshift, missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.89
• Publications: 1 publications found

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]

ADGRG2 Gene-Disease associations (from GenCC):

• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286724 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 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-19003070-CACAG-TCT is Pathogenic according to our data. Variant chrX-19003070-CACAG-TCT is described in ClinVar as Pathogenic. ClinVar VariationId is 253014.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079858.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG2	NM_001079858.3	MANE Select	c.2002_2006delCTGTGinsAGA	p.Leu668ArgfsTer21	frameshift missense	Exon 24 of 29	NP_001073327.1
	ADGRG2	NM_005756.4		c.1993_1997delCTGTGinsAGA	p.Leu665ArgfsTer21	frameshift missense	Exon 24 of 29	NP_005747.2
	ADGRG2	NM_001079859.3		c.1960_1964delCTGTGinsAGA	p.Leu654ArgfsTer21	frameshift missense	Exon 23 of 28	NP_001073328.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG2	ENST00000379869.8	TSL:1 MANE Select	c.2002_2006delCTGTGinsAGA	p.Leu668ArgfsTer21	frameshift missense	Exon 24 of 29	ENSP00000369198.3
	ADGRG2	ENST00000357991.7	TSL:1	c.1993_1997delCTGTGinsAGA	p.Leu665ArgfsTer21	frameshift missense	Exon 24 of 29	ENSP00000350680.3
	ADGRG2	ENST00000356606.8	TSL:1	c.1960_1964delCTGTGinsAGA	p.Leu654ArgfsTer21	frameshift missense	Exon 23 of 28	ENSP00000349015.4

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Vas deferens, congenital bilateral aplasia of, X-linked Pathogenic:1

May 24, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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

Apr 12, 2016

Biology Pathology Center, Lille University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879255539; hg19: chrX-19021188;