Genetic Variant ADGRG2:c.-2+234C>G (chrX-19082468-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001079858.3(ADGRG2):c.-2+234C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 110,462 control chromosomes in the GnomAD database, including 8,142 homozygotes. There are 12,518 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 8142 hom., 12518 hem., cov: 22)

Consequence

ADGRG2
NM_001079858.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRG2	NM_001079858.3	MANE Select	c.-2+234C>G	intron	N/A	NP_001073327.1
ADGRG2	NM_005756.4		c.-2+234C>G	intron	N/A	NP_005747.2
ADGRG2	NM_001079859.3		c.-2+234C>G	intron	N/A	NP_001073328.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRG2	ENST00000379869.8	TSL:1 MANE Select	c.-2+234C>G	intron	N/A	ENSP00000369198.3
ADGRG2	ENST00000357991.7	TSL:1	c.-2+234C>G	intron	N/A	ENSP00000350680.3
ADGRG2	ENST00000356606.8	TSL:1	c.-2+234C>G	intron	N/A	ENSP00000349015.4

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

43516

AN:

110408

Hom.:

8135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.317

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.351

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

GnomAD4 genome

AF:

0.394

AC:

43570

AN:

110462

Hom.:

8142

Cov.:

AF XY:

0.382

AC XY:

12518

AN XY:

32750

show subpopulations

African (AFR)

AF:

0.733

AC:

22169

AN:

30236

American (AMR)

AF:

0.391

AC:

4029

AN:

10304

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

581

AN:

2647

East Asian (EAS)

AF:

0.445

AC:

1550

AN:

3483

South Asian (SAS)

AF:

0.358

AC:

933

AN:

2606

European-Finnish (FIN)

AF:

0.222

AC:

1303

AN:

5862

Middle Eastern (MID)

AF:

0.324

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.230

AC:

12160

AN:

52939

Other (OTH)

AF:

0.357

AC:

533

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

749

1498

2248

2997

3746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.302

Hom.:

1938

Bravo

AF:

0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.1

(source)

DANN

Benign

0.66

PhyloP100

-0.027

PromoterAI

-0.0017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over