rs879255539

Positions:

• chrX-19003069-ACACAG-ATCT

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_2006delinsAGA​(p.Leu668ArgfsTer21) variant causes a frameshift 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
• 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]

(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/exons	MANE	Protein	UniProt
ADGRG2	NM_001079858.3	c.2002_2006delinsAGA	p.Leu668ArgfsTer21	frameshift_variant	24/29	ENST00000379869.8	NP_001073327.1
LOC101928415	XR_001755805.2	n.755+14729_755+14733delinsTCT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8	c.2002_2006delinsAGA	p.Leu668ArgfsTer21	frameshift_variant	24/29	1	NM_001079858.3	ENSP00000369198	A1
	ENST00000662768.1	n.229+18417_229+18421delinsTCT		intron_variant, non_coding_transcript_variant

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

Pathogenic, no assertion criteria provided

literature only

OMIM

May 24, 2024

- -

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

Pathogenic, criteria provided, single submitter

clinical testing

Biology Pathology Center, Lille University Hospital

Apr 12, 2016

- -

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;