chr7-88125600-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001324418.2(ADAM22):c.619G>A(p.Val207Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,590,260 control chromosomes in the GnomAD database, including 2,605 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 (no stars).

Frequency

Genomes: 𝑓 0.067 ( 429 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2176 hom. )

Consequence

ADAM22
NM_001324418.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.11

Publications

20 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001481235).

BP6

Variant 7-88125600-G-A is Benign according to our data. Variant chr7-88125600-G-A is described in ClinVar as [Benign]. Clinvar id is 3060180.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM22	NM_001324418.2 link	c.619G>A	p.Val207Ile	missense_variant	Exon 8 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.619G>A	p.Val207Ile	missense_variant	Exon 8 of 32	5	NM_001324418.2	ENSP00000412085.2		H7C3I4

Frequencies

GnomAD3 genomes

AF:

0.0672

AC:

10204

AN:

151942

Hom.:

421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0904

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0439

Gnomad OTH

AF:

0.0789

GnomAD2 exomes

AF:

0.0650

AC:

15149

AN:

232904

AF XY:

0.0611

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0274

Gnomad FIN exome

AF:

0.0651

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0634

GnomAD4 exome

AF:

0.0475

AC:

68315

AN:

1438202

Hom.:

2176

Cov.:

AF XY:

0.0475

AC XY:

33963

AN XY:

715438

show subpopulations

African (AFR)

AF:

0.0878

AC:

2802

AN:

31924

American (AMR)

AF:

0.141

AC:

5704

AN:

40460

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2626

AN:

25608

East Asian (EAS)

AF:

0.0242

AC:

936

AN:

38710

South Asian (SAS)

AF:

0.0610

AC:

5047

AN:

82750

European-Finnish (FIN)

AF:

0.0616

AC:

3272

AN:

53140

Middle Eastern (MID)

AF:

0.0881

AC:

501

AN:

5688

European-Non Finnish (NFE)

AF:

0.0400

AC:

44018

AN:

1100390

Other (OTH)

AF:

0.0573

AC:

3409

AN:

59532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

2749

5499

8248

10998

13747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0674

AC:

10243

AN:

152058

Hom.:

429

Cov.:

AF XY:

0.0681

AC XY:

5060

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0906

AC:

3762

AN:

41520

American (AMR)

AF:

0.113

AC:

1716

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3466

East Asian (EAS)

AF:

0.0282

AC:

146

AN:

5176

South Asian (SAS)

AF:

0.0611

AC:

295

AN:

4826

European-Finnish (FIN)

AF:

0.0673

AC:

713

AN:

10600

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0439

AC:

2983

AN:

67920

Other (OTH)

AF:

0.0824

AC:

174

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

482

965

1447

1930

2412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0512

Hom.:

1026

Bravo

AF:

0.0728

TwinsUK

AF:

0.0442

AC:

164

ALSPAC

AF:

0.0407

AC:

157

ESP6500AA

AF:

0.0856

AC:

309

ESP6500EA

AF:

0.0463

AC:

377

ExAC

AF:

0.0639

AC:

7713

Asia WGS

AF:

0.0700

AC:

242

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADAM22-related disorder

Benign:1

Apr 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.010

.;T;.;T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.84

T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;.;N;N;N;.

PhyloP100

1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.090

N;N;N;N;N;N

REVEL

Benign

0.055

Sift

Benign

0.29

T;T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;B;.

Vest4

0.091

MPC

0.40

ClinPred

0.0099

GERP RS

1.4

Varity_R

0.034

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr7-88125600-G-A

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