Variant 7-87935182-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 14/20 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, single submitter B:1

Conservation

PhyloP100: -0.991

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
ADAM22	NM_001324418.2 linkuse as main transcript	c.242C>G	p.Pro81Arg	missense_variant	2/32	ENST00000413139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM22	ENST00000413139.2 linkuse as main transcript	c.242C>G	p.Pro81Arg	missense_variant	2/32	5	NM_001324418.2	A2

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

GnomAD3 exomes

AF:

0.537

AC:

118346

AN:

220508

Hom.:

32951

AF XY:

0.523

AC XY:

63389

AN XY:

121302

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 SAS exome

AF:

0.369

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

Gnomad4 AFR exome

AF:

0.927

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.536

Gnomad4 NFE exome

AF:

0.510

Gnomad4 OTH exome

AF:

0.534

GnomAD4 genome

AF:

0.631

AC:

95797

AN:

151900

Hom.:

32682

Cov.:

AF XY:

0.626

AC XY:

46439

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.912

Gnomad4 AMR

AF:

0.595

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.633

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 61

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

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;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

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

Varity_R

0.049

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over