Genetic Variant NM_032777.10: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:

Genome browser will be placed here

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032777.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA2	NM_032777.10	MANE Select	c.411-30A>G		intron	N/A	NP_116166.9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRA2	ENST00000412232.3	TSL:1 MANE Select	c.411-30A>G	intron	N/A	ENSP00000406367.2
ADGRA2	ENST00000315215.11	TSL:1	c.411-30A>G	intron	N/A	ENSP00000323508.7
ADGRA2	ENST00000428068.5	TSL:3	c.285-30A>G	intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over