Genetic Variant ADGRG2:p.Glu516fs (chrX-19008000-C-CA) – ACMG Classification: Pathogenic (12 pts)

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001079858.3(ADGRG2):c.1545dupT(p.Glu516fs) variant causes a frameshift change involving the alteration of a non-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)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ADGRG2
NM_001079858.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

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:

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ACMG classification

Classification was made for transcript

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-19008000-C-CA is Pathogenic according to our data. Variant chrX-19008000-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 253015.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 link	c.1545dupT	p.Glu516fs	frameshift_variant	Exon 19 of 29	ENST00000379869.8	NP_001073327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8 link	c.1545dupT	p.Glu516fs	frameshift_variant	Exon 19 of 29	1	NM_001079858.3	ENSP00000369198.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1091421

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357269

African (AFR)

AF:

0.00

AC:

AN:

26177

American (AMR)

AF:

0.00

AC:

AN:

34474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19229

East Asian (EAS)

AF:

0.00

AC:

AN:

30068

South Asian (SAS)

AF:

0.00

AC:

AN:

52807

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838225

Other (OTH)

AF:

0.00

AC:

AN:

45845

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vas deferens, congenital bilateral aplasia of, X-linked

Pathogenic:1

Sep 30, 2016

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

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X-19008000-CA-CAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over