rs879255539

Variant names:

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

Variant summary

Our verdict is Pathogenic. Variant got 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

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]

ENSG00000286724 (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-19003070-CACAG-TCT is Pathogenic according to our data. Variant chrX-19003070-CACAG-TCT is described in ClinVar as [Pathogenic]. Clinvar id is 253014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG2	NM_001079858.3	c.2002_2006delCTGTGinsAGA	p.Leu668ArgfsTer21	frameshift_variant, missense_variant	Exon 24 of 29	ENST00000379869.8	NP_001073327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8	c.2002_2006delCTGTGinsAGA	p.Leu668ArgfsTer21	frameshift_variant, missense_variant	Exon 24 of 29	1	NM_001079858.3	ENSP00000369198.3

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

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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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs879255539; hg19: chrX-19021188;