Genetic Variant ADGRA2:c.411-30A>G (chr8-37829231-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032777.10(ADGRA2):c.411-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,586,536 control chromosomes in the GnomAD database, including 511,766 homozygotes. 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 0.84 ( 53981 hom., cov: 26)

Exomes 𝑓: 0.80 ( 457785 hom. )

Consequence

ADGRA2
NM_032777.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.98

Publications

18 publications found

Variant links:

Genes affected

ADGRA2 (HGNC:17849): (adhesion G protein-coupled receptor A2) Predicted to enable G protein-coupled receptor activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ADGRA2 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ADGRA2	NM_032777.10 link	c.411-30A>G	intron_variant	Intron 3 of 18	ENST00000412232.3	NP_116166.9
ADGRA2	XM_011544481.3 link	c.411-30A>G	intron_variant	Intron 3 of 18		XP_011542783.1
ADGRA2	XM_011544482.3 link	c.339-30A>G	intron_variant	Intron 2 of 17		XP_011542784.1
ADGRA2	XM_011544483.3 link	c.411-30A>G	intron_variant	Intron 3 of 17		XP_011542785.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ADGRA2	ENST00000412232.3 link	c.411-30A>G	intron_variant	Intron 3 of 18	1	NM_032777.10	ENSP00000406367.2
ADGRA2	ENST00000315215.11 link	c.411-30A>G	intron_variant	Intron 3 of 15	1		ENSP00000323508.7
ADGRA2	ENST00000428068.5 link	c.285-30A>G	intron_variant	Intron 3 of 5	3		ENSP00000400860.1

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127040

AN:

151084

Hom.:

53922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.946

Gnomad AMI

AF:

0.905

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.868

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.794

Gnomad OTH

AF:

0.806

GnomAD2 exomes

AF:

0.812

AC:

203883

AN:

251066

AF XY:

0.804

show subpopulations

Gnomad AFR exome

AF:

0.947

Gnomad AMR exome

AF:

0.845

Gnomad ASJ exome

AF:

0.679

Gnomad EAS exome

AF:

0.862

Gnomad FIN exome

AF:

0.853

Gnomad NFE exome

AF:

0.789

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.797

AC:

1144255

AN:

1435332

Hom.:

457785

Cov.:

AF XY:

0.796

AC XY:

569859

AN XY:

715810

show subpopulations

African (AFR)

AF:

0.950

AC:

31329

AN:

32970

American (AMR)

AF:

0.840

AC:

37526

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

17782

AN:

25968

East Asian (EAS)

AF:

0.868

AC:

34364

AN:

39578

South Asian (SAS)

AF:

0.774

AC:

66347

AN:

85714

European-Finnish (FIN)

AF:

0.851

AC:

45319

AN:

53244

Middle Eastern (MID)

AF:

0.662

AC:

3786

AN:

5720

European-Non Finnish (NFE)

AF:

0.791

AC:

860813

AN:

1087980

Other (OTH)

AF:

0.790

AC:

46989

AN:

59466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

12159

24318

36476

48635

60794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20076

40152

60228

80304

100380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.841

AC:

127160

AN:

151204

Hom.:

53981

Cov.:

AF XY:

0.842

AC XY:

62101

AN XY:

73782

show subpopulations

African (AFR)

AF:

0.946

AC:

38949

AN:

41170

American (AMR)

AF:

0.805

AC:

12235

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2312

AN:

3462

East Asian (EAS)

AF:

0.869

AC:

4400

AN:

5066

South Asian (SAS)

AF:

0.791

AC:

3738

AN:

4728

European-Finnish (FIN)

AF:

0.854

AC:

8956

AN:

10490

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.794

AC:

53851

AN:

67790

Other (OTH)

AF:

0.806

AC:

1695

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

940

1881

2821

3762

4702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.803

Hom.:

214147

Bravo

AF:

0.846

Asia WGS

AF:

0.824

AC:

2865

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0040

(source)

DANN

Benign

0.46

PhyloP100

-6.0

Mutation Taster

=12/88

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over