7-87935182-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001324418.2(ADAM22):c.242C>G(p.Pro81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,600,082 control chromosomes in the GnomAD database, including 230,061 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P81A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.63 ( 32682 hom., cov: 30)

Exomes 𝑓: 0.52 ( 197379 hom. )

Consequence

ADAM22
NM_001324418.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.991

Publications

32 publications found

Variant links:

Genes affected

ADAM22 (HGNC:201): (ADAM metallopeptidase domain 22) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Unlike other members of the ADAM protein family, the protein encoded by this gene lacks metalloprotease activity since it has no zinc-binding motif. This gene is highly expressed in the brain and may function as an integrin ligand in the brain. In mice, it has been shown to be essential for correct myelination in the peripheral nervous system. Alternative splicing results in several transcript variants.[provided by RefSeq, Dec 2010]

ADAM22 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 61
Inheritance: Unknown, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ADAM22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7454687E-7).

BP6

Variant 7-87935182-C-G is Benign according to our data. Variant chr7-87935182-C-G is described in ClinVar as [Benign]. Clinvar id is 1188945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM22	NM_001324418.2 link	c.242C>G	p.Pro81Arg	missense_variant	Exon 2 of 32	ENST00000413139.2	NP_001311347.1	H7C3I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM22	ENST00000413139.2 link	c.242C>G	p.Pro81Arg	missense_variant	Exon 2 of 32	5	NM_001324418.2	ENSP00000412085.2		H7C3I4

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95658

AN:

151782

Hom.:

32609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.912

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.634

GnomAD2 exomes

AF:

0.537

AC:

118346

AN:

220508

AF XY:

0.523

show subpopulations

Gnomad AFR exome

AF:

0.922

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.516

AC:

747885

AN:

1448182

Hom.:

197379

Cov.:

AF XY:

0.510

AC XY:

367020

AN XY:

719120

show subpopulations

African (AFR)

AF:

0.927

AC:

30876

AN:

33290

American (AMR)

AF:

0.561

AC:

24173

AN:

43060

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14620

AN:

25644

East Asian (EAS)

AF:

0.546

AC:

21564

AN:

39478

South Asian (SAS)

AF:

0.366

AC:

31104

AN:

85046

European-Finnish (FIN)

AF:

0.536

AC:

27618

AN:

51518

Middle Eastern (MID)

AF:

0.534

AC:

2985

AN:

5590

European-Non Finnish (NFE)

AF:

0.510

AC:

563044

AN:

1104790

Other (OTH)

AF:

0.534

AC:

31901

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

20403

40806

61209

81612

102015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16456

32912

49368

65824

82280

<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:

0.631

AC:

95797

AN:

151900

Hom.:

32682

Cov.:

AF XY:

0.626

AC XY:

46439

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.912

AC:

37841

AN:

41498

American (AMR)

AF:

0.595

AC:

9093

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1983

AN:

3470

East Asian (EAS)

AF:

0.540

AC:

2758

AN:

5104

South Asian (SAS)

AF:

0.370

AC:

1777

AN:

4806

European-Finnish (FIN)

AF:

0.532

AC:

5610

AN:

10536

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34768

AN:

67896

Other (OTH)

AF:

0.633

AC:

1334

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1558

3117

4675

6234

7792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.493

Hom.:

2674

Bravo

AF:

0.649

TwinsUK

AF:

0.502

AC:

1862

ALSPAC

AF:

0.506

AC:

1952

ESP6500AA

AF:

0.892

AC:

3375

ESP6500EA

AF:

0.516

AC:

4227

ExAC

AF:

0.527

AC:

62567

Asia WGS

AF:

0.487

AC:

1699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 61

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.84

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0038

.;T;T;.;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.012

T;T;T;T;T;T;T

MetaRNN

Benign

6.7e-7

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

L;.;.;L;L;L;.

PhyloP100

-0.99

PrimateAI

Benign

0.26

PROVEAN

Benign

0.36

N;N;N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.67

T;T;T;T;T;T;T

Sift4G

Benign

0.70

T;T;T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B;B;.

Vest4

0.032

MPC

0.53

ClinPred

0.0023

GERP RS

-5.3

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.049

gMVP

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over