Variant chr7-87934559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001324418.2(ADAM22):c.85+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,604,206 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 42 hom. )

Consequence

ADAM22
NM_001324418.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.825

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:

ADAM22 (HGNC:):

ADAM22 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-87934559-G-A is Benign according to our data. Variant chr7-87934559-G-A is described in ClinVar as [Benign]. Clinvar id is 773743.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-87934559-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00238 (362/152264) while in subpopulation EAS AF= 0.0404 (208/5154). AF 95% confidence interval is 0.0359. There are 7 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM22	NM_001324418.2 linkuse as main transcript	c.85+9G>A		intron_variant		ENST00000413139.2	NP_001311347.1	H7C3I4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM22	ENST00000413139.2 linkuse as main transcript	c.85+9G>A		intron_variant		5	NM_001324418.2	ENSP00000412085.2		H7C3I4

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0405

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00990

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00424

AC:

971

AN:

228960

Hom.:

AF XY:

0.00397

AC XY:

499

AN XY:

125540

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0388

Gnomad SAS exome

AF:

0.00161

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.000648

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00173

AC:

2519

AN:

1451942

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1261

AN XY:

722174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0377

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.00919

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.00238

AC:

362

AN:

152264

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0404

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00990

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000443

Hom.:

Bravo

AF:

0.00199

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

ADAM22-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2024

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.4

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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