dbSNP rs774488954: ADGRG2:p.Phe515LeufsTer17 (chrX-19008000-CA-C) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001079858.3(ADGRG2):c.1545delT(p.Phe515LeufsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ADGRG2
NM_001079858.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

Publications

2 publications found

Variant links:

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

ADGRG2 links:

ENSG00000286724 (HGNC:):

ENSG00000286724 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG2	NM_001079858.3 link	c.1545delT	p.Phe515LeufsTer17	frameshift_variant	Exon 19 of 29	ENST00000379869.8	NP_001073327.1	Q8IZP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8 link	c.1545delT	p.Phe515LeufsTer17	frameshift_variant	Exon 19 of 29	1	NM_001079858.3	ENSP00000369198.3		Q8IZP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1091288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357152

African (AFR)

AF:

0.00

AC:

AN:

26172

American (AMR)

AF:

0.00

AC:

AN:

34466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19226

East Asian (EAS)

AF:

0.00

AC:

AN:

30066

South Asian (SAS)

AF:

0.00

AC:

AN:

52799

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40487

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838123

Other (OTH)

AF:

0.00

AC:

AN:

45841

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over